Acis e Galatéia
Galateia, nereide de alva pele, espero-te nesta praia, ao romper da alva, sedento de teus beijos doces e salgados; de passar os meus dedos pelos teus cabelos loiros e deles tirar alguma conchinha, algas, um sargo, camarões-de-moçambique, holutúrias, lesmas-do-mar ou mesmo fataças e chaputas. Quis Neptuno, que benévola onda te arrastasse despreocupada e brincando puerilmente na espuma, para meu regaço e o meu coração ficasse tolhido por teus olhos lânguidos, por teus seios pequenos, pela tua glabrescente e rechonchuda crica. Não sei se te lavas por baixo amiúde, mas também não faz mal, pois o acre cheiro a maresia que exala a tua natureza bem podia ser do mar e, o que gosto de a lamber até se me gastarem as papilas gustativas e rasgar o freio da língua. Alimentas-te de peixes e alforrecas, eu sei, não fossem as muitas espinhas espetadas na verga, que cato durante semanas a fio, de infectadas pústulas na glande, depois de ter arrombado, durante horas a fio, teu apertado e renitente traseiro. Mas não faz mal, deixa. Pelo menos não temos um filho com cara de bacalhau.
Eu, Polifemo, bruto ciclope de um só olho, ainda recordo a lancinante dor do espeto em brasa com que Ulisses, rei de Ítaca, em seus desmandes marítimos, aportando a minha ilha me logrou assim cegar. Mesmo na escuridão sinto teu cheiro Galateia. Faz-me vontade de comer uma lascada de bacalhau, não sei porquê. Urro solitário pelo teu amor e imagino-te sugando com sons de chupantes engasgos este meu insalubre marsapo enquanto borbotões de meu sémen te congestionam a epiglote, e eu zuca! Zuca! Zuca…Agarrando-te pelas orelhas te vou empurrando a cabeça contra a raiz do pénis, afocinhando-te nos tomates. Mato Acis, teu amante, pois morro de ciúme! Surpreendê-lo-ei na praia e enfiar-lhe-ei naqueles cornos de camafeu um pesado bajolo de granito, eh, eh, eh…até que os seus parcos miolos de fornicador de pescadas se espalhem sobre o espraiar das ondas. Assim, farei, ah, ah, ah!...
Oh doce amante, Ácis, que tua verga hirta não sentirei mais arrepelando-me o grelo até ao colo do útero. Era fininha e mal me tocava cá os badalos de meu cono, mas eu gostava de ti: teus cabelos aos caracóis, teu peito depilado, o teu rabo redondo e esse estranho hábito de me chupares o hemorroidal. Ah choro o meu amado e maldigo o monstro Polifemo! Corre o sangue de Acis, que Neptuno ora por divina piedade, transforma em rio, perdendo-se nas águas do mar, oh agora púrpura Talassa, para me lembrar sempre de sua triste desventura.
Por amor acometi tão vil acto, Galateia e repara neste nabo grosso, que pende de minha rústica tanga de ciclope. Repara nestas veias, que túrgidas, me sobressaem do escroto. Pulsa minha odorífera glande, quase esguichando translúcida langonha, tal o tesão que sinto por ti, ninfa do mar!
Sim…vendo melhor, é grosso…sim senhor e os colhões parecem duas abóboras-porqueiras. Talvez possa experimentar só um bocadinho; deixá-las amassar-me as bordas estimulando-lhes a circulação. Sim, isso, mais, mais, …oh…mete mais fundo…oooh…corre-te em meu vazadoiro! Ai!...ai….(geme)…ah…é Natal!...É Nataaal!....uuh…uhhh….uhhhh…é Nataaaaaaaal!....
‘Toma lá um presentinho, minha renazinha!’
Revirando os olhos, larga grossa torrente de espumosa e fétida langonha que esguicha em fabuloso jorro, com tanta força que Galateia desencava do gigantesco nabo e é projectada de costas para as ondas onde Neptuno a aguardava de pila em riste, empalando-a. Oh Neptuno, maroto…é Natal, mas não estava á espera de me ver sentada na árvore, com a estrela a fazer-me cócegas no cólon transverso, com bolas vermelhas e luzidiase, luzinhas a piscarem-me na pintelheira…(suspira).
‘Luzinhas?’…Ele há cada uma. São uns protozoários luminescentes, acho. Gonyaulax polyedra, acho eu…’
‘Foda-se. Chato do caralho. Põe-me mas é a tripa a piscar e cala-te, velho jarreta’.
sexta-feira, 5 de dezembro de 2008
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Originally published In Press as doi:10.1074/jbc.M111818200 on February 21, 2002
J. Biol. Chem., Vol. 277, Issue 18, 15795-15800, May 3, 2002
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Two Defective Heterozygous Luteinizing Hormone Receptors Can Rescue Hormone Action*
ChangWoo LeeDagger , Inhae JiDagger , KiSung RyuDagger , YongSang SongDagger , P. Michael Conn§, and Tae H. JiDagger ¶
From the Dagger Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506-0055 and the § Oregon Regional Primate Research Center and Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, Oregon 97201
Luteinizing hormone receptor is a G protein-coupled receptor and consists of two halves: the N-terminal extracellular half (exodomain) and C-terminal membrane-associated half (endodomain). Hormone binds to the exodomain, and the resulting hormone-exodomain complex modulates the endodomain to generate signals. There are mutations that impair either hormone binding or signal generation. We report that the coexpression of a binding defective mutant and a signal-defective mutant rescues signal generation to produce cAMP. This rescue requires both types of mutant receptors and is dependent on the human chorionic gonadotropin dose, the surface concentration of mutant receptors, and the amino acid position of mutations. Furthermore, random collisions among mutant receptors are not involved in the rescue. Our observations provide new insights into the mechanisms of the functional and structural relationship of the exo- and endodomain, signal transduction, and receptor genetics, in particular for defective heterozygotes.
* This work was supported by Grants HD-18702 and DK-51469 from the National Institutes of Health.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
¶ To whom correspondence should be addressed: Dept. of Chemistry, University of Kentucky, Lexington, KY 40506-0055. Tel.: 859-257-3163; Fax: 859-257-3229; E-mail: tji@uky.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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Hetero-oligomerization between {beta}2- and {beta}3-Adrenergic Receptors Generates a {beta}-Adrenergic Signaling Unit with Distinct Functional Properties
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Trans-Activation of Mutant Follicle-Stimulating Hormone Receptors Selectively Generates Only One of Two Hormone Signals
Mol. Endocrinol., April 1, 2004; 18(4): 968 - 978.
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A. Ulloa-Aguirre, J. A. Janovick, A. Leanos-Miranda, and P. M. Conn
Misrouted cell surface GnRH receptors as a disease aetiology for congenital isolated hypogonadotrophic hypogonadism
Hum. Reprod. Update, March 1, 2004; 10(2): 177 - 192.
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Constitutive and Agonist-dependent Self-association of the Cell Surface Human Lutropin Receptor
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Dominant-Negative Action of Disease-Causing Gonadotropin-Releasing Hormone Receptor (GnRHR) Mutants: A Trait That Potentially Coevolved with Decreased Plasma Membrane Expression of GnRHR in Humans
J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3360 - 3367.
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Originally published In Press as doi:10.1074/jbc.M111818200 on February 21, 2002
J. Biol. Chem., Vol. 277, Issue 18, 15795-15800, May 3, 2002
This Article
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Two Defective Heterozygous Luteinizing Hormone Receptors Can Rescue Hormone Action*
ChangWoo LeeDagger , Inhae JiDagger , KiSung RyuDagger , YongSang SongDagger , P. Michael Conn§, and Tae H. JiDagger ¶
From the Dagger Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506-0055 and the § Oregon Regional Primate Research Center and Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, Oregon 97201
Luteinizing hormone receptor is a G protein-coupled receptor and consists of two halves: the N-terminal extracellular half (exodomain) and C-terminal membrane-associated half (endodomain). Hormone binds to the exodomain, and the resulting hormone-exodomain complex modulates the endodomain to generate signals. There are mutations that impair either hormone binding or signal generation. We report that the coexpression of a binding defective mutant and a signal-defective mutant rescues signal generation to produce cAMP. This rescue requires both types of mutant receptors and is dependent on the human chorionic gonadotropin dose, the surface concentration of mutant receptors, and the amino acid position of mutations. Furthermore, random collisions among mutant receptors are not involved in the rescue. Our observations provide new insights into the mechanisms of the functional and structural relationship of the exo- and endodomain, signal transduction, and receptor genetics, in particular for defective heterozygotes.
* This work was supported by Grants HD-18702 and DK-51469 from the National Institutes of Health.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
¶ To whom correspondence should be addressed: Dept. of Chemistry, University of Kentucky, Lexington, KY 40506-0055. Tel.: 859-257-3163; Fax: 859-257-3229; E-mail: tji@uky.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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This article has been cited by other articles:
Home page
Mol. Pharmacol.Home page
A. Breit, K. Gagnidze, L. A. Devi, M. Lagace, and M. Bouvier
Simultaneous Activation of the {delta} Opioid Receptor ({delta}OR)/Sensory Neuron-Specific Receptor-4 (SNSR-4) Hetero-Oligomer by the Mixed Bivalent Agonist Bovine Adrenal Medulla Peptide 22 Activates SNSR-4 but Inhibits {delta}OR Signaling
Mol. Pharmacol., August 1, 2006; 70(2): 686 - 696.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
G. Pascal and G. Milligan
Functional Complementation and the Analysis of Opioid Receptor Homodimerization
Mol. Pharmacol., September 1, 2005; 68(3): 905 - 915.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
D. Mesnier and J.-L. Baneres
Cooperative Conformational Changes in a G-protein-coupled Receptor Dimer, the Leukotriene B4 Receptor BLT1
J. Biol. Chem., November 26, 2004; 279(48): 49664 - 49670.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
J. J. Carrillo, J. F. Lopez-Gimenez, and G. Milligan
Multiple Interactions between Transmembrane Helices Generate the Oligomeric {alpha}1b-Adrenoceptor
Mol. Pharmacol., November 1, 2004; 66(5): 1123 - 1137.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
A. Breit, M. Lagace, and M. Bouvier
Hetero-oligomerization between {beta}2- and {beta}3-Adrenergic Receptors Generates a {beta}-Adrenergic Signaling Unit with Distinct Functional Properties
J. Biol. Chem., July 2, 2004; 279(27): 28756 - 28765.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
G. Milligan
G Protein-Coupled Receptor Dimerization: Function and Ligand Pharmacology
Mol. Pharmacol., July 1, 2004; 66(1): 1 - 7.
[Abstract] [Full Text] [PDF]
Home page
Mol. Endocrinol.Home page
I. Ji, C. Lee, M. Jeoung, Y. Koo, G. A. Sievert, and T. H. Ji
Trans-Activation of Mutant Follicle-Stimulating Hormone Receptors Selectively Generates Only One of Two Hormone Signals
Mol. Endocrinol., April 1, 2004; 18(4): 968 - 978.
[Abstract] [Full Text] [PDF]
Home page
Hum Reprod UpdateHome page
A. Ulloa-Aguirre, J. A. Janovick, A. Leanos-Miranda, and P. M. Conn
Misrouted cell surface GnRH receptors as a disease aetiology for congenital isolated hypogonadotrophic hypogonadism
Hum. Reprod. Update, March 1, 2004; 10(2): 177 - 192.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
Y.-X. Tao, N. B. Johnson, and D. L. Segaloff
Constitutive and Agonist-dependent Self-association of the Cell Surface Human Lutropin Receptor
J. Biol. Chem., February 13, 2004; 279(7): 5904 - 5914.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
J. J. Carrillo, J. Pediani, and G. Milligan
Dimers of Class A G Protein-coupled Receptors Function via Agonist-mediated Trans-activation of Associated G Proteins
J. Biol. Chem., October 24, 2003; 278(43): 42578 - 42587.
[Abstract] [Full Text] [PDF]
Home page
J. Clin. Endocrinol. Metab.Home page
A. Leanos-Miranda, A. Ulloa-Aguirre, T. H. Ji, J. A. Janovick, and P. M. Conn
Dominant-Negative Action of Disease-Causing Gonadotropin-Releasing Hormone Receptor (GnRHR) Mutants: A Trait That Potentially Coevolved with Decreased Plasma Membrane Expression of GnRHR in Humans
J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3360 - 3367.
[Abstract] [Full Text] [PDF]
Home page
Mol. Endocrinol.Home page
P. Narayan, J. Gray, and D. Puett
Yoked Complexes of Human Choriogonadotropin and the Lutropin Receptor: Evidence that Monomeric Individual Subunits Are Inactive
Mol. Endocrinol., December 1, 2002; 16(12): 2733 - 2745.
[Abstract] [Full Text] [PDF]
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Originally published In Press as doi:10.1074/jbc.M111818200 on February 21, 2002
J. Biol. Chem., Vol. 277, Issue 18, 15795-15800, May 3, 2002
This Article
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What's this?
Two Defective Heterozygous Luteinizing Hormone Receptors Can Rescue Hormone Action*
ChangWoo LeeDagger , Inhae JiDagger , KiSung RyuDagger , YongSang SongDagger , P. Michael Conn§, and Tae H. JiDagger ¶
From the Dagger Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506-0055 and the § Oregon Regional Primate Research Center and Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, Oregon 97201
Luteinizing hormone receptor is a G protein-coupled receptor and consists of two halves: the N-terminal extracellular half (exodomain) and C-terminal membrane-associated half (endodomain). Hormone binds to the exodomain, and the resulting hormone-exodomain complex modulates the endodomain to generate signals. There are mutations that impair either hormone binding or signal generation. We report that the coexpression of a binding defective mutant and a signal-defective mutant rescues signal generation to produce cAMP. This rescue requires both types of mutant receptors and is dependent on the human chorionic gonadotropin dose, the surface concentration of mutant receptors, and the amino acid position of mutations. Furthermore, random collisions among mutant receptors are not involved in the rescue. Our observations provide new insights into the mechanisms of the functional and structural relationship of the exo- and endodomain, signal transduction, and receptor genetics, in particular for defective heterozygotes.
* This work was supported by Grants HD-18702 and DK-51469 from the National Institutes of Health.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
¶ To whom correspondence should be addressed: Dept. of Chemistry, University of Kentucky, Lexington, KY 40506-0055. Tel.: 859-257-3163; Fax: 859-257-3229; E-mail: tji@uky.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?
This article has been cited by other articles:
Home page
Mol. Pharmacol.Home page
A. Breit, K. Gagnidze, L. A. Devi, M. Lagace, and M. Bouvier
Simultaneous Activation of the {delta} Opioid Receptor ({delta}OR)/Sensory Neuron-Specific Receptor-4 (SNSR-4) Hetero-Oligomer by the Mixed Bivalent Agonist Bovine Adrenal Medulla Peptide 22 Activates SNSR-4 but Inhibits {delta}OR Signaling
Mol. Pharmacol., August 1, 2006; 70(2): 686 - 696.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
G. Pascal and G. Milligan
Functional Complementation and the Analysis of Opioid Receptor Homodimerization
Mol. Pharmacol., September 1, 2005; 68(3): 905 - 915.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
D. Mesnier and J.-L. Baneres
Cooperative Conformational Changes in a G-protein-coupled Receptor Dimer, the Leukotriene B4 Receptor BLT1
J. Biol. Chem., November 26, 2004; 279(48): 49664 - 49670.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
J. J. Carrillo, J. F. Lopez-Gimenez, and G. Milligan
Multiple Interactions between Transmembrane Helices Generate the Oligomeric {alpha}1b-Adrenoceptor
Mol. Pharmacol., November 1, 2004; 66(5): 1123 - 1137.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
A. Breit, M. Lagace, and M. Bouvier
Hetero-oligomerization between {beta}2- and {beta}3-Adrenergic Receptors Generates a {beta}-Adrenergic Signaling Unit with Distinct Functional Properties
J. Biol. Chem., July 2, 2004; 279(27): 28756 - 28765.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
G. Milligan
G Protein-Coupled Receptor Dimerization: Function and Ligand Pharmacology
Mol. Pharmacol., July 1, 2004; 66(1): 1 - 7.
[Abstract] [Full Text] [PDF]
Home page
Mol. Endocrinol.Home page
I. Ji, C. Lee, M. Jeoung, Y. Koo, G. A. Sievert, and T. H. Ji
Trans-Activation of Mutant Follicle-Stimulating Hormone Receptors Selectively Generates Only One of Two Hormone Signals
Mol. Endocrinol., April 1, 2004; 18(4): 968 - 978.
[Abstract] [Full Text] [PDF]
Home page
Hum Reprod UpdateHome page
A. Ulloa-Aguirre, J. A. Janovick, A. Leanos-Miranda, and P. M. Conn
Misrouted cell surface GnRH receptors as a disease aetiology for congenital isolated hypogonadotrophic hypogonadism
Hum. Reprod. Update, March 1, 2004; 10(2): 177 - 192.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
Y.-X. Tao, N. B. Johnson, and D. L. Segaloff
Constitutive and Agonist-dependent Self-association of the Cell Surface Human Lutropin Receptor
J. Biol. Chem., February 13, 2004; 279(7): 5904 - 5914.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
J. J. Carrillo, J. Pediani, and G. Milligan
Dimers of Class A G Protein-coupled Receptors Function via Agonist-mediated Trans-activation of Associated G Proteins
J. Biol. Chem., October 24, 2003; 278(43): 42578 - 42587.
[Abstract] [Full Text] [PDF]
Home page
J. Clin. Endocrinol. Metab.Home page
A. Leanos-Miranda, A. Ulloa-Aguirre, T. H. Ji, J. A. Janovick, and P. M. Conn
Dominant-Negative Action of Disease-Causing Gonadotropin-Releasing Hormone Receptor (GnRHR) Mutants: A Trait That Potentially Coevolved with Decreased Plasma Membrane Expression of GnRHR in Humans
J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3360 - 3367.
[Abstract] [Full Text] [PDF]
Home page
Mol. Endocrinol.Home page
P. Narayan, J. Gray, and D. Puett
Yoked Complexes of Human Choriogonadotropin and the Lutropin Receptor: Evidence that Monomeric Individual Subunits Are Inactive
Mol. Endocrinol., December 1, 2002; 16(12): 2733 - 2745.
[Abstract] [Full Text] [PDF]
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Two Defective Heterozygous Luteinizing Hormone Receptors Can Rescue Hormone Action*
ChangWoo LeeDagger , Inhae JiDagger , KiSung RyuDagger , YongSang SongDagger , P. Michael Conn§, and Tae H. JiDagger ¶
From the Dagger Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506-0055 and the § Oregon Regional Primate Research Center and Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, Oregon 97201
Luteinizing hormone receptor is a G protein-coupled receptor and consists of two halves: the N-terminal extracellular half (exodomain) and C-terminal membrane-associated half (endodomain). Hormone binds to the exodomain, and the resulting hormone-exodomain complex modulates the endodomain to generate signals. There are mutations that impair either hormone binding or signal generation. We report that the coexpression of a binding defective mutant and a signal-defective mutant rescues signal generation to produce cAMP. This rescue requires both types of mutant receptors and is dependent on the human chorionic gonadotropin dose, the surface concentration of mutant receptors, and the amino acid position of mutations. Furthermore, random collisions among mutant receptors are not involved in the rescue. Our observations provide new insights into the mechanisms of the functional and structural relationship of the exo- and endodomain, signal transduction, and receptor genetics, in particular for defective heterozygotes.
* This work was supported by Grants HD-18702 and DK-51469 from the National Institutes of Health.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
¶ To whom correspondence should be addressed: Dept. of Chemistry, University of Kentucky, Lexington, KY 40506-0055. Tel.: 859-257-3163; Fax: 859-257-3229; E-mail: tji@uky.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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Simultaneous Activation of the {delta} Opioid Receptor ({delta}OR)/Sensory Neuron-Specific Receptor-4 (SNSR-4) Hetero-Oligomer by the Mixed Bivalent Agonist Bovine Adrenal Medulla Peptide 22 Activates SNSR-4 but Inhibits {delta}OR Signaling
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Cooperative Conformational Changes in a G-protein-coupled Receptor Dimer, the Leukotriene B4 Receptor BLT1
J. Biol. Chem., November 26, 2004; 279(48): 49664 - 49670.
[Abstract] [Full Text] [PDF]
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J. J. Carrillo, J. F. Lopez-Gimenez, and G. Milligan
Multiple Interactions between Transmembrane Helices Generate the Oligomeric {alpha}1b-Adrenoceptor
Mol. Pharmacol., November 1, 2004; 66(5): 1123 - 1137.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
A. Breit, M. Lagace, and M. Bouvier
Hetero-oligomerization between {beta}2- and {beta}3-Adrenergic Receptors Generates a {beta}-Adrenergic Signaling Unit with Distinct Functional Properties
J. Biol. Chem., July 2, 2004; 279(27): 28756 - 28765.
[Abstract] [Full Text] [PDF]
Home page
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G Protein-Coupled Receptor Dimerization: Function and Ligand Pharmacology
Mol. Pharmacol., July 1, 2004; 66(1): 1 - 7.
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I. Ji, C. Lee, M. Jeoung, Y. Koo, G. A. Sievert, and T. H. Ji
Trans-Activation of Mutant Follicle-Stimulating Hormone Receptors Selectively Generates Only One of Two Hormone Signals
Mol. Endocrinol., April 1, 2004; 18(4): 968 - 978.
[Abstract] [Full Text] [PDF]
Home page
Hum Reprod UpdateHome page
A. Ulloa-Aguirre, J. A. Janovick, A. Leanos-Miranda, and P. M. Conn
Misrouted cell surface GnRH receptors as a disease aetiology for congenital isolated hypogonadotrophic hypogonadism
Hum. Reprod. Update, March 1, 2004; 10(2): 177 - 192.
[Abstract] [Full Text] [PDF]
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Y.-X. Tao, N. B. Johnson, and D. L. Segaloff
Constitutive and Agonist-dependent Self-association of the Cell Surface Human Lutropin Receptor
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[Abstract] [Full Text] [PDF]
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Dimers of Class A G Protein-coupled Receptors Function via Agonist-mediated Trans-activation of Associated G Proteins
J. Biol. Chem., October 24, 2003; 278(43): 42578 - 42587.
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Home page
J. Clin. Endocrinol. Metab.Home page
A. Leanos-Miranda, A. Ulloa-Aguirre, T. H. Ji, J. A. Janovick, and P. M. Conn
Dominant-Negative Action of Disease-Causing Gonadotropin-Releasing Hormone Receptor (GnRHR) Mutants: A Trait That Potentially Coevolved with Decreased Plasma Membrane Expression of GnRHR in Humans
J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3360 - 3367.
[Abstract] [Full Text] [PDF]
Home page
Mol. Endocrinol.Home page
P. Narayan, J. Gray, and D. Puett
Yoked Complexes of Human Choriogonadotropin and the Lutropin Receptor: Evidence that Monomeric Individual Subunits Are Inactive
Mol. Endocrinol., December 1, 2002; 16(12): 2733 - 2745.
[Abstract] [Full Text] [PDF]
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Originally published In Press as doi:10.1074/jbc.M111818200 on February 21, 2002
J. Biol. Chem., Vol. 277, Issue 18, 15795-15800, May 3, 2002
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Two Defective Heterozygous Luteinizing Hormone Receptors Can Rescue Hormone Action*
ChangWoo LeeDagger , Inhae JiDagger , KiSung RyuDagger , YongSang SongDagger , P. Michael Conn§, and Tae H. JiDagger ¶
From the Dagger Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506-0055 and the § Oregon Regional Primate Research Center and Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, Oregon 97201
Luteinizing hormone receptor is a G protein-coupled receptor and consists of two halves: the N-terminal extracellular half (exodomain) and C-terminal membrane-associated half (endodomain). Hormone binds to the exodomain, and the resulting hormone-exodomain complex modulates the endodomain to generate signals. There are mutations that impair either hormone binding or signal generation. We report that the coexpression of a binding defective mutant and a signal-defective mutant rescues signal generation to produce cAMP. This rescue requires both types of mutant receptors and is dependent on the human chorionic gonadotropin dose, the surface concentration of mutant receptors, and the amino acid position of mutations. Furthermore, random collisions among mutant receptors are not involved in the rescue. Our observations provide new insights into the mechanisms of the functional and structural relationship of the exo- and endodomain, signal transduction, and receptor genetics, in particular for defective heterozygotes.
* This work was supported by Grants HD-18702 and DK-51469 from the National Institutes of Health.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
¶ To whom correspondence should be addressed: Dept. of Chemistry, University of Kentucky, Lexington, KY 40506-0055. Tel.: 859-257-3163; Fax: 859-257-3229; E-mail: tji@uky.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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Home page
Mol. Pharmacol.Home page
A. Breit, K. Gagnidze, L. A. Devi, M. Lagace, and M. Bouvier
Simultaneous Activation of the {delta} Opioid Receptor ({delta}OR)/Sensory Neuron-Specific Receptor-4 (SNSR-4) Hetero-Oligomer by the Mixed Bivalent Agonist Bovine Adrenal Medulla Peptide 22 Activates SNSR-4 but Inhibits {delta}OR Signaling
Mol. Pharmacol., August 1, 2006; 70(2): 686 - 696.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
G. Pascal and G. Milligan
Functional Complementation and the Analysis of Opioid Receptor Homodimerization
Mol. Pharmacol., September 1, 2005; 68(3): 905 - 915.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
D. Mesnier and J.-L. Baneres
Cooperative Conformational Changes in a G-protein-coupled Receptor Dimer, the Leukotriene B4 Receptor BLT1
J. Biol. Chem., November 26, 2004; 279(48): 49664 - 49670.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
J. J. Carrillo, J. F. Lopez-Gimenez, and G. Milligan
Multiple Interactions between Transmembrane Helices Generate the Oligomeric {alpha}1b-Adrenoceptor
Mol. Pharmacol., November 1, 2004; 66(5): 1123 - 1137.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
A. Breit, M. Lagace, and M. Bouvier
Hetero-oligomerization between {beta}2- and {beta}3-Adrenergic Receptors Generates a {beta}-Adrenergic Signaling Unit with Distinct Functional Properties
J. Biol. Chem., July 2, 2004; 279(27): 28756 - 28765.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
G. Milligan
G Protein-Coupled Receptor Dimerization: Function and Ligand Pharmacology
Mol. Pharmacol., July 1, 2004; 66(1): 1 - 7.
[Abstract] [Full Text] [PDF]
Home page
Mol. Endocrinol.Home page
I. Ji, C. Lee, M. Jeoung, Y. Koo, G. A. Sievert, and T. H. Ji
Trans-Activation of Mutant Follicle-Stimulating Hormone Receptors Selectively Generates Only One of Two Hormone Signals
Mol. Endocrinol., April 1, 2004; 18(4): 968 - 978.
[Abstract] [Full Text] [PDF]
Home page
Hum Reprod UpdateHome page
A. Ulloa-Aguirre, J. A. Janovick, A. Leanos-Miranda, and P. M. Conn
Misrouted cell surface GnRH receptors as a disease aetiology for congenital isolated hypogonadotrophic hypogonadism
Hum. Reprod. Update, March 1, 2004; 10(2): 177 - 192.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
Y.-X. Tao, N. B. Johnson, and D. L. Segaloff
Constitutive and Agonist-dependent Self-association of the Cell Surface Human Lutropin Receptor
J. Biol. Chem., February 13, 2004; 279(7): 5904 - 5914.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
J. J. Carrillo, J. Pediani, and G. Milligan
Dimers of Class A G Protein-coupled Receptors Function via Agonist-mediated Trans-activation of Associated G Proteins
J. Biol. Chem., October 24, 2003; 278(43): 42578 - 42587.
[Abstract] [Full Text] [PDF]
Home page
J. Clin. Endocrinol. Metab.Home page
A. Leanos-Miranda, A. Ulloa-Aguirre, T. H. Ji, J. A. Janovick, and P. M. Conn
Dominant-Negative Action of Disease-Causing Gonadotropin-Releasing Hormone Receptor (GnRHR) Mutants: A Trait That Potentially Coevolved with Decreased Plasma Membrane Expression of GnRHR in Humans
J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3360 - 3367.
[Abstract] [Full Text] [PDF]
Home page
Mol. Endocrinol.Home page
P. Narayan, J. Gray, and D. Puett
Yoked Complexes of Human Choriogonadotropin and the Lutropin Receptor: Evidence that Monomeric Individual Subunits Are Inactive
Mol. Endocrinol., December 1, 2002; 16(12): 2733 - 2745.
[Abstract] [Full Text] [PDF]
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Originally published In Press as doi:10.1074/jbc.M111818200 on February 21, 2002
J. Biol. Chem., Vol. 277, Issue 18, 15795-15800, May 3, 2002
This Article
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What's this?
Two Defective Heterozygous Luteinizing Hormone Receptors Can Rescue Hormone Action*
ChangWoo LeeDagger , Inhae JiDagger , KiSung RyuDagger , YongSang SongDagger , P. Michael Conn§, and Tae H. JiDagger ¶
From the Dagger Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506-0055 and the § Oregon Regional Primate Research Center and Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, Oregon 97201
Luteinizing hormone receptor is a G protein-coupled receptor and consists of two halves: the N-terminal extracellular half (exodomain) and C-terminal membrane-associated half (endodomain). Hormone binds to the exodomain, and the resulting hormone-exodomain complex modulates the endodomain to generate signals. There are mutations that impair either hormone binding or signal generation. We report that the coexpression of a binding defective mutant and a signal-defective mutant rescues signal generation to produce cAMP. This rescue requires both types of mutant receptors and is dependent on the human chorionic gonadotropin dose, the surface concentration of mutant receptors, and the amino acid position of mutations. Furthermore, random collisions among mutant receptors are not involved in the rescue. Our observations provide new insights into the mechanisms of the functional and structural relationship of the exo- and endodomain, signal transduction, and receptor genetics, in particular for defective heterozygotes.
* This work was supported by Grants HD-18702 and DK-51469 from the National Institutes of Health.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
¶ To whom correspondence should be addressed: Dept. of Chemistry, University of Kentucky, Lexington, KY 40506-0055. Tel.: 859-257-3163; Fax: 859-257-3229; E-mail: tji@uky.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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Home page
Mol. Pharmacol.Home page
A. Breit, K. Gagnidze, L. A. Devi, M. Lagace, and M. Bouvier
Simultaneous Activation of the {delta} Opioid Receptor ({delta}OR)/Sensory Neuron-Specific Receptor-4 (SNSR-4) Hetero-Oligomer by the Mixed Bivalent Agonist Bovine Adrenal Medulla Peptide 22 Activates SNSR-4 but Inhibits {delta}OR Signaling
Mol. Pharmacol., August 1, 2006; 70(2): 686 - 696.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
G. Pascal and G. Milligan
Functional Complementation and the Analysis of Opioid Receptor Homodimerization
Mol. Pharmacol., September 1, 2005; 68(3): 905 - 915.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
D. Mesnier and J.-L. Baneres
Cooperative Conformational Changes in a G-protein-coupled Receptor Dimer, the Leukotriene B4 Receptor BLT1
J. Biol. Chem., November 26, 2004; 279(48): 49664 - 49670.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
J. J. Carrillo, J. F. Lopez-Gimenez, and G. Milligan
Multiple Interactions between Transmembrane Helices Generate the Oligomeric {alpha}1b-Adrenoceptor
Mol. Pharmacol., November 1, 2004; 66(5): 1123 - 1137.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
A. Breit, M. Lagace, and M. Bouvier
Hetero-oligomerization between {beta}2- and {beta}3-Adrenergic Receptors Generates a {beta}-Adrenergic Signaling Unit with Distinct Functional Properties
J. Biol. Chem., July 2, 2004; 279(27): 28756 - 28765.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
G. Milligan
G Protein-Coupled Receptor Dimerization: Function and Ligand Pharmacology
Mol. Pharmacol., July 1, 2004; 66(1): 1 - 7.
[Abstract] [Full Text] [PDF]
Home page
Mol. Endocrinol.Home page
I. Ji, C. Lee, M. Jeoung, Y. Koo, G. A. Sievert, and T. H. Ji
Trans-Activation of Mutant Follicle-Stimulating Hormone Receptors Selectively Generates Only One of Two Hormone Signals
Mol. Endocrinol., April 1, 2004; 18(4): 968 - 978.
[Abstract] [Full Text] [PDF]
Home page
Hum Reprod UpdateHome page
A. Ulloa-Aguirre, J. A. Janovick, A. Leanos-Miranda, and P. M. Conn
Misrouted cell surface GnRH receptors as a disease aetiology for congenital isolated hypogonadotrophic hypogonadism
Hum. Reprod. Update, March 1, 2004; 10(2): 177 - 192.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
Y.-X. Tao, N. B. Johnson, and D. L. Segaloff
Constitutive and Agonist-dependent Self-association of the Cell Surface Human Lutropin Receptor
J. Biol. Chem., February 13, 2004; 279(7): 5904 - 5914.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
J. J. Carrillo, J. Pediani, and G. Milligan
Dimers of Class A G Protein-coupled Receptors Function via Agonist-mediated Trans-activation of Associated G Proteins
J. Biol. Chem., October 24, 2003; 278(43): 42578 - 42587.
[Abstract] [Full Text] [PDF]
Home page
J. Clin. Endocrinol. Metab.Home page
A. Leanos-Miranda, A. Ulloa-Aguirre, T. H. Ji, J. A. Janovick, and P. M. Conn
Dominant-Negative Action of Disease-Causing Gonadotropin-Releasing Hormone Receptor (GnRHR) Mutants: A Trait That Potentially Coevolved with Decreased Plasma Membrane Expression of GnRHR in Humans
J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3360 - 3367.
[Abstract] [Full Text] [PDF]
Home page
Mol. Endocrinol.Home page
P. Narayan, J. Gray, and D. Puett
Yoked Complexes of Human Choriogonadotropin and the Lutropin Receptor: Evidence that Monomeric Individual Subunits Are Inactive
Mol. Endocrinol., December 1, 2002; 16(12): 2733 - 2745.
[Abstract] [Full Text] [PDF]
BC Avanti Polar Lipids
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Originally published In Press as doi:10.1074/jbc.M111818200 on February 21, 2002
J. Biol. Chem., Vol. 277, Issue 18, 15795-15800, May 3, 2002
This Article
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Two Defective Heterozygous Luteinizing Hormone Receptors Can Rescue Hormone Action*
ChangWoo LeeDagger , Inhae JiDagger , KiSung RyuDagger , YongSang SongDagger , P. Michael Conn§, and Tae H. JiDagger ¶
From the Dagger Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506-0055 and the § Oregon Regional Primate Research Center and Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, Oregon 97201
Luteinizing hormone receptor is a G protein-coupled receptor and consists of two halves: the N-terminal extracellular half (exodomain) and C-terminal membrane-associated half (endodomain). Hormone binds to the exodomain, and the resulting hormone-exodomain complex modulates the endodomain to generate signals. There are mutations that impair either hormone binding or signal generation. We report that the coexpression of a binding defective mutant and a signal-defective mutant rescues signal generation to produce cAMP. This rescue requires both types of mutant receptors and is dependent on the human chorionic gonadotropin dose, the surface concentration of mutant receptors, and the amino acid position of mutations. Furthermore, random collisions among mutant receptors are not involved in the rescue. Our observations provide new insights into the mechanisms of the functional and structural relationship of the exo- and endodomain, signal transduction, and receptor genetics, in particular for defective heterozygotes.
* This work was supported by Grants HD-18702 and DK-51469 from the National Institutes of Health.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
¶ To whom correspondence should be addressed: Dept. of Chemistry, University of Kentucky, Lexington, KY 40506-0055. Tel.: 859-257-3163; Fax: 859-257-3229; E-mail: tji@uky.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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Home page
Mol. Pharmacol.Home page
A. Breit, K. Gagnidze, L. A. Devi, M. Lagace, and M. Bouvier
Simultaneous Activation of the {delta} Opioid Receptor ({delta}OR)/Sensory Neuron-Specific Receptor-4 (SNSR-4) Hetero-Oligomer by the Mixed Bivalent Agonist Bovine Adrenal Medulla Peptide 22 Activates SNSR-4 but Inhibits {delta}OR Signaling
Mol. Pharmacol., August 1, 2006; 70(2): 686 - 696.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
G. Pascal and G. Milligan
Functional Complementation and the Analysis of Opioid Receptor Homodimerization
Mol. Pharmacol., September 1, 2005; 68(3): 905 - 915.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
D. Mesnier and J.-L. Baneres
Cooperative Conformational Changes in a G-protein-coupled Receptor Dimer, the Leukotriene B4 Receptor BLT1
J. Biol. Chem., November 26, 2004; 279(48): 49664 - 49670.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
J. J. Carrillo, J. F. Lopez-Gimenez, and G. Milligan
Multiple Interactions between Transmembrane Helices Generate the Oligomeric {alpha}1b-Adrenoceptor
Mol. Pharmacol., November 1, 2004; 66(5): 1123 - 1137.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
A. Breit, M. Lagace, and M. Bouvier
Hetero-oligomerization between {beta}2- and {beta}3-Adrenergic Receptors Generates a {beta}-Adrenergic Signaling Unit with Distinct Functional Properties
J. Biol. Chem., July 2, 2004; 279(27): 28756 - 28765.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
G. Milligan
G Protein-Coupled Receptor Dimerization: Function and Ligand Pharmacology
Mol. Pharmacol., July 1, 2004; 66(1): 1 - 7.
[Abstract] [Full Text] [PDF]
Home page
Mol. Endocrinol.Home page
I. Ji, C. Lee, M. Jeoung, Y. Koo, G. A. Sievert, and T. H. Ji
Trans-Activation of Mutant Follicle-Stimulating Hormone Receptors Selectively Generates Only One of Two Hormone Signals
Mol. Endocrinol., April 1, 2004; 18(4): 968 - 978.
[Abstract] [Full Text] [PDF]
Home page
Hum Reprod UpdateHome page
A. Ulloa-Aguirre, J. A. Janovick, A. Leanos-Miranda, and P. M. Conn
Misrouted cell surface GnRH receptors as a disease aetiology for congenital isolated hypogonadotrophic hypogonadism
Hum. Reprod. Update, March 1, 2004; 10(2): 177 - 192.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
Y.-X. Tao, N. B. Johnson, and D. L. Segaloff
Constitutive and Agonist-dependent Self-association of the Cell Surface Human Lutropin Receptor
J. Biol. Chem., February 13, 2004; 279(7): 5904 - 5914.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
J. J. Carrillo, J. Pediani, and G. Milligan
Dimers of Class A G Protein-coupled Receptors Function via Agonist-mediated Trans-activation of Associated G Proteins
J. Biol. Chem., October 24, 2003; 278(43): 42578 - 42587.
[Abstract] [Full Text] [PDF]
Home page
J. Clin. Endocrinol. Metab.Home page
A. Leanos-Miranda, A. Ulloa-Aguirre, T. H. Ji, J. A. Janovick, and P. M. Conn
Dominant-Negative Action of Disease-Causing Gonadotropin-Releasing Hormone Receptor (GnRHR) Mutants: A Trait That Potentially Coevolved with Decreased Plasma Membrane Expression of GnRHR in Humans
J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3360 - 3367.
[Abstract] [Full Text] [PDF]
Home page
Mol. Endocrinol.Home page
P. Narayan, J. Gray, and D. Puett
Yoked Complexes of Human Choriogonadotropin and the Lutropin Receptor: Evidence that Monomeric Individual Subunits Are Inactive
Mol. Endocrinol., December 1, 2002; 16(12): 2733 - 2745.
[Abstract] [Full Text] [PDF]
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J. Biol. Chem., Vol. 277, Issue 18, 15795-15800, May 3, 2002
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Two Defective Heterozygous Luteinizing Hormone Receptors Can Rescue Hormone Action*
ChangWoo LeeDagger , Inhae JiDagger , KiSung RyuDagger , YongSang SongDagger , P. Michael Conn§, and Tae H. JiDagger ¶
From the Dagger Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506-0055 and the § Oregon Regional Primate Research Center and Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, Oregon 97201
Luteinizing hormone receptor is a G protein-coupled receptor and consists of two halves: the N-terminal extracellular half (exodomain) and C-terminal membrane-associated half (endodomain). Hormone binds to the exodomain, and the resulting hormone-exodomain complex modulates the endodomain to generate signals. There are mutations that impair either hormone binding or signal generation. We report that the coexpression of a binding defective mutant and a signal-defective mutant rescues signal generation to produce cAMP. This rescue requires both types of mutant receptors and is dependent on the human chorionic gonadotropin dose, the surface concentration of mutant receptors, and the amino acid position of mutations. Furthermore, random collisions among mutant receptors are not involved in the rescue. Our observations provide new insights into the mechanisms of the functional and structural relationship of the exo- and endodomain, signal transduction, and receptor genetics, in particular for defective heterozygotes.
* This work was supported by Grants HD-18702 and DK-51469 from the National Institutes of Health.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
¶ To whom correspondence should be addressed: Dept. of Chemistry, University of Kentucky, Lexington, KY 40506-0055. Tel.: 859-257-3163; Fax: 859-257-3229; E-mail: tji@uky.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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Home page
Mol. Pharmacol.Home page
A. Breit, K. Gagnidze, L. A. Devi, M. Lagace, and M. Bouvier
Simultaneous Activation of the {delta} Opioid Receptor ({delta}OR)/Sensory Neuron-Specific Receptor-4 (SNSR-4) Hetero-Oligomer by the Mixed Bivalent Agonist Bovine Adrenal Medulla Peptide 22 Activates SNSR-4 but Inhibits {delta}OR Signaling
Mol. Pharmacol., August 1, 2006; 70(2): 686 - 696.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
G. Pascal and G. Milligan
Functional Complementation and the Analysis of Opioid Receptor Homodimerization
Mol. Pharmacol., September 1, 2005; 68(3): 905 - 915.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
D. Mesnier and J.-L. Baneres
Cooperative Conformational Changes in a G-protein-coupled Receptor Dimer, the Leukotriene B4 Receptor BLT1
J. Biol. Chem., November 26, 2004; 279(48): 49664 - 49670.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
J. J. Carrillo, J. F. Lopez-Gimenez, and G. Milligan
Multiple Interactions between Transmembrane Helices Generate the Oligomeric {alpha}1b-Adrenoceptor
Mol. Pharmacol., November 1, 2004; 66(5): 1123 - 1137.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
A. Breit, M. Lagace, and M. Bouvier
Hetero-oligomerization between {beta}2- and {beta}3-Adrenergic Receptors Generates a {beta}-Adrenergic Signaling Unit with Distinct Functional Properties
J. Biol. Chem., July 2, 2004; 279(27): 28756 - 28765.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
G. Milligan
G Protein-Coupled Receptor Dimerization: Function and Ligand Pharmacology
Mol. Pharmacol., July 1, 2004; 66(1): 1 - 7.
[Abstract] [Full Text] [PDF]
Home page
Mol. Endocrinol.Home page
I. Ji, C. Lee, M. Jeoung, Y. Koo, G. A. Sievert, and T. H. Ji
Trans-Activation of Mutant Follicle-Stimulating Hormone Receptors Selectively Generates Only One of Two Hormone Signals
Mol. Endocrinol., April 1, 2004; 18(4): 968 - 978.
[Abstract] [Full Text] [PDF]
Home page
Hum Reprod UpdateHome page
A. Ulloa-Aguirre, J. A. Janovick, A. Leanos-Miranda, and P. M. Conn
Misrouted cell surface GnRH receptors as a disease aetiology for congenital isolated hypogonadotrophic hypogonadism
Hum. Reprod. Update, March 1, 2004; 10(2): 177 - 192.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
Y.-X. Tao, N. B. Johnson, and D. L. Segaloff
Constitutive and Agonist-dependent Self-association of the Cell Surface Human Lutropin Receptor
J. Biol. Chem., February 13, 2004; 279(7): 5904 - 5914.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
J. J. Carrillo, J. Pediani, and G. Milligan
Dimers of Class A G Protein-coupled Receptors Function via Agonist-mediated Trans-activation of Associated G Proteins
J. Biol. Chem., October 24, 2003; 278(43): 42578 - 42587.
[Abstract] [Full Text] [PDF]
Home page
J. Clin. Endocrinol. Metab.Home page
A. Leanos-Miranda, A. Ulloa-Aguirre, T. H. Ji, J. A. Janovick, and P. M. Conn
Dominant-Negative Action of Disease-Causing Gonadotropin-Releasing Hormone Receptor (GnRHR) Mutants: A Trait That Potentially Coevolved with Decreased Plasma Membrane Expression of GnRHR in Humans
J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3360 - 3367.
[Abstract] [Full Text] [PDF]
Home page
Mol. Endocrinol.Home page
P. Narayan, J. Gray, and D. Puett
Yoked Complexes of Human Choriogonadotropin and the Lutropin Receptor: Evidence that Monomeric Individual Subunits Are Inactive
Mol. Endocrinol., December 1, 2002; 16(12): 2733 - 2745.
[Abstract] [Full Text] [PDF]
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Originally published In Press as doi:10.1074/jbc.M111818200 on February 21, 2002
J. Biol. Chem., Vol. 277, Issue 18, 15795-15800, May 3, 2002
This Article
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Two Defective Heterozygous Luteinizing Hormone Receptors Can Rescue Hormone Action*
ChangWoo LeeDagger , Inhae JiDagger , KiSung RyuDagger , YongSang SongDagger , P. Michael Conn§, and Tae H. JiDagger ¶
From the Dagger Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506-0055 and the § Oregon Regional Primate Research Center and Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, Oregon 97201
Luteinizing hormone receptor is a G protein-coupled receptor and consists of two halves: the N-terminal extracellular half (exodomain) and C-terminal membrane-associated half (endodomain). Hormone binds to the exodomain, and the resulting hormone-exodomain complex modulates the endodomain to generate signals. There are mutations that impair either hormone binding or signal generation. We report that the coexpression of a binding defective mutant and a signal-defective mutant rescues signal generation to produce cAMP. This rescue requires both types of mutant receptors and is dependent on the human chorionic gonadotropin dose, the surface concentration of mutant receptors, and the amino acid position of mutations. Furthermore, random collisions among mutant receptors are not involved in the rescue. Our observations provide new insights into the mechanisms of the functional and structural relationship of the exo- and endodomain, signal transduction, and receptor genetics, in particular for defective heterozygotes.
* This work was supported by Grants HD-18702 and DK-51469 from the National Institutes of Health.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
¶ To whom correspondence should be addressed: Dept. of Chemistry, University of Kentucky, Lexington, KY 40506-0055. Tel.: 859-257-3163; Fax: 859-257-3229; E-mail: tji@uky.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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This article has been cited by other articles:
Home page
Mol. Pharmacol.Home page
A. Breit, K. Gagnidze, L. A. Devi, M. Lagace, and M. Bouvier
Simultaneous Activation of the {delta} Opioid Receptor ({delta}OR)/Sensory Neuron-Specific Receptor-4 (SNSR-4) Hetero-Oligomer by the Mixed Bivalent Agonist Bovine Adrenal Medulla Peptide 22 Activates SNSR-4 but Inhibits {delta}OR Signaling
Mol. Pharmacol., August 1, 2006; 70(2): 686 - 696.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
G. Pascal and G. Milligan
Functional Complementation and the Analysis of Opioid Receptor Homodimerization
Mol. Pharmacol., September 1, 2005; 68(3): 905 - 915.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
D. Mesnier and J.-L. Baneres
Cooperative Conformational Changes in a G-protein-coupled Receptor Dimer, the Leukotriene B4 Receptor BLT1
J. Biol. Chem., November 26, 2004; 279(48): 49664 - 49670.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
J. J. Carrillo, J. F. Lopez-Gimenez, and G. Milligan
Multiple Interactions between Transmembrane Helices Generate the Oligomeric {alpha}1b-Adrenoceptor
Mol. Pharmacol., November 1, 2004; 66(5): 1123 - 1137.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
A. Breit, M. Lagace, and M. Bouvier
Hetero-oligomerization between {beta}2- and {beta}3-Adrenergic Receptors Generates a {beta}-Adrenergic Signaling Unit with Distinct Functional Properties
J. Biol. Chem., July 2, 2004; 279(27): 28756 - 28765.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
G. Milligan
G Protein-Coupled Receptor Dimerization: Function and Ligand Pharmacology
Mol. Pharmacol., July 1, 2004; 66(1): 1 - 7.
[Abstract] [Full Text] [PDF]
Home page
Mol. Endocrinol.Home page
I. Ji, C. Lee, M. Jeoung, Y. Koo, G. A. Sievert, and T. H. Ji
Trans-Activation of Mutant Follicle-Stimulating Hormone Receptors Selectively Generates Only One of Two Hormone Signals
Mol. Endocrinol., April 1, 2004; 18(4): 968 - 978.
[Abstract] [Full Text] [PDF]
Home page
Hum Reprod UpdateHome page
A. Ulloa-Aguirre, J. A. Janovick, A. Leanos-Miranda, and P. M. Conn
Misrouted cell surface GnRH receptors as a disease aetiology for congenital isolated hypogonadotrophic hypogonadism
Hum. Reprod. Update, March 1, 2004; 10(2): 177 - 192.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
Y.-X. Tao, N. B. Johnson, and D. L. Segaloff
Constitutive and Agonist-dependent Self-association of the Cell Surface Human Lutropin Receptor
J. Biol. Chem., February 13, 2004; 279(7): 5904 - 5914.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
J. J. Carrillo, J. Pediani, and G. Milligan
Dimers of Class A G Protein-coupled Receptors Function via Agonist-mediated Trans-activation of Associated G Proteins
J. Biol. Chem., October 24, 2003; 278(43): 42578 - 42587.
[Abstract] [Full Text] [PDF]
Home page
J. Clin. Endocrinol. Metab.Home page
A. Leanos-Miranda, A. Ulloa-Aguirre, T. H. Ji, J. A. Janovick, and P. M. Conn
Dominant-Negative Action of Disease-Causing Gonadotropin-Releasing Hormone Receptor (GnRHR) Mutants: A Trait That Potentially Coevolved with Decreased Plasma Membrane Expression of GnRHR in Humans
J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3360 - 3367.
[Abstract] [Full Text] [PDF]
Home page
Mol. Endocrinol.Home page
P. Narayan, J. Gray, and D. Puett
Yoked Complexes of Human Choriogonadotropin and the Lutropin Receptor: Evidence that Monomeric Individual Subunits Are Inactive
Mol. Endocrinol., December 1, 2002; 16(12): 2733 - 2745.
[Abstract] [Full Text] [PDF]
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Originally published In Press as doi:10.1074/jbc.M111818200 on February 21, 2002
J. Biol. Chem., Vol. 277, Issue 18, 15795-15800, May 3, 2002
This Article
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What's this?
Two Defective Heterozygous Luteinizing Hormone Receptors Can Rescue Hormone Action*
ChangWoo LeeDagger , Inhae JiDagger , KiSung RyuDagger , YongSang SongDagger , P. Michael Conn§, and Tae H. JiDagger ¶
From the Dagger Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506-0055 and the § Oregon Regional Primate Research Center and Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, Oregon 97201
Luteinizing hormone receptor is a G protein-coupled receptor and consists of two halves: the N-terminal extracellular half (exodomain) and C-terminal membrane-associated half (endodomain). Hormone binds to the exodomain, and the resulting hormone-exodomain complex modulates the endodomain to generate signals. There are mutations that impair either hormone binding or signal generation. We report that the coexpression of a binding defective mutant and a signal-defective mutant rescues signal generation to produce cAMP. This rescue requires both types of mutant receptors and is dependent on the human chorionic gonadotropin dose, the surface concentration of mutant receptors, and the amino acid position of mutations. Furthermore, random collisions among mutant receptors are not involved in the rescue. Our observations provide new insights into the mechanisms of the functional and structural relationship of the exo- and endodomain, signal transduction, and receptor genetics, in particular for defective heterozygotes.
* This work was supported by Grants HD-18702 and DK-51469 from the National Institutes of Health.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
¶ To whom correspondence should be addressed: Dept. of Chemistry, University of Kentucky, Lexington, KY 40506-0055. Tel.: 859-257-3163; Fax: 859-257-3229; E-mail: tji@uky.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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This article has been cited by other articles:
Home page
Mol. Pharmacol.Home page
A. Breit, K. Gagnidze, L. A. Devi, M. Lagace, and M. Bouvier
Simultaneous Activation of the {delta} Opioid Receptor ({delta}OR)/Sensory Neuron-Specific Receptor-4 (SNSR-4) Hetero-Oligomer by the Mixed Bivalent Agonist Bovine Adrenal Medulla Peptide 22 Activates SNSR-4 but Inhibits {delta}OR Signaling
Mol. Pharmacol., August 1, 2006; 70(2): 686 - 696.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
G. Pascal and G. Milligan
Functional Complementation and the Analysis of Opioid Receptor Homodimerization
Mol. Pharmacol., September 1, 2005; 68(3): 905 - 915.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
D. Mesnier and J.-L. Baneres
Cooperative Conformational Changes in a G-protein-coupled Receptor Dimer, the Leukotriene B4 Receptor BLT1
J. Biol. Chem., November 26, 2004; 279(48): 49664 - 49670.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
J. J. Carrillo, J. F. Lopez-Gimenez, and G. Milligan
Multiple Interactions between Transmembrane Helices Generate the Oligomeric {alpha}1b-Adrenoceptor
Mol. Pharmacol., November 1, 2004; 66(5): 1123 - 1137.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
A. Breit, M. Lagace, and M. Bouvier
Hetero-oligomerization between {beta}2- and {beta}3-Adrenergic Receptors Generates a {beta}-Adrenergic Signaling Unit with Distinct Functional Properties
J. Biol. Chem., July 2, 2004; 279(27): 28756 - 28765.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
G. Milligan
G Protein-Coupled Receptor Dimerization: Function and Ligand Pharmacology
Mol. Pharmacol., July 1, 2004; 66(1): 1 - 7.
[Abstract] [Full Text] [PDF]
Home page
Mol. Endocrinol.Home page
I. Ji, C. Lee, M. Jeoung, Y. Koo, G. A. Sievert, and T. H. Ji
Trans-Activation of Mutant Follicle-Stimulating Hormone Receptors Selectively Generates Only One of Two Hormone Signals
Mol. Endocrinol., April 1, 2004; 18(4): 968 - 978.
[Abstract] [Full Text] [PDF]
Home page
Hum Reprod UpdateHome page
A. Ulloa-Aguirre, J. A. Janovick, A. Leanos-Miranda, and P. M. Conn
Misrouted cell surface GnRH receptors as a disease aetiology for congenital isolated hypogonadotrophic hypogonadism
Hum. Reprod. Update, March 1, 2004; 10(2): 177 - 192.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
Y.-X. Tao, N. B. Johnson, and D. L. Segaloff
Constitutive and Agonist-dependent Self-association of the Cell Surface Human Lutropin Receptor
J. Biol. Chem., February 13, 2004; 279(7): 5904 - 5914.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
J. J. Carrillo, J. Pediani, and G. Milligan
Dimers of Class A G Protein-coupled Receptors Function via Agonist-mediated Trans-activation of Associated G Proteins
J. Biol. Chem., October 24, 2003; 278(43): 42578 - 42587.
[Abstract] [Full Text] [PDF]
Home page
J. Clin. Endocrinol. Metab.Home page
A. Leanos-Miranda, A. Ulloa-Aguirre, T. H. Ji, J. A. Janovick, and P. M. Conn
Dominant-Negative Action of Disease-Causing Gonadotropin-Releasing Hormone Receptor (GnRHR) Mutants: A Trait That Potentially Coevolved with Decreased Plasma Membrane Expression of GnRHR in Humans
J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3360 - 3367.
[Abstract] [Full Text] [PDF]
Home page
Mol. Endocrinol.Home page
P. Narayan, J. Gray, and D. Puett
Yoked Complexes of Human Choriogonadotropin and the Lutropin Receptor: Evidence that Monomeric Individual Subunits Are Inactive
Mol. Endocrinol., December 1, 2002; 16(12): 2733 - 2745.
[Abstract] [Full Text] [PDF]
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
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Originally published In Press as doi:10.1074/jbc.M111818200 on February 21, 2002
J. Biol. Chem., Vol. 277, Issue 18, 15795-15800, May 3, 2002
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Two Defective Heterozygous Luteinizing Hormone Receptors Can Rescue Hormone Action*
ChangWoo LeeDagger , Inhae JiDagger , KiSung RyuDagger , YongSang SongDagger , P. Michael Conn§, and Tae H. JiDagger ¶
From the Dagger Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506-0055 and the § Oregon Regional Primate Research Center and Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, Oregon 97201
Luteinizing hormone receptor is a G protein-coupled receptor and consists of two halves: the N-terminal extracellular half (exodomain) and C-terminal membrane-associated half (endodomain). Hormone binds to the exodomain, and the resulting hormone-exodomain complex modulates the endodomain to generate signals. There are mutations that impair either hormone binding or signal generation. We report that the coexpression of a binding defective mutant and a signal-defective mutant rescues signal generation to produce cAMP. This rescue requires both types of mutant receptors and is dependent on the human chorionic gonadotropin dose, the surface concentration of mutant receptors, and the amino acid position of mutations. Furthermore, random collisions among mutant receptors are not involved in the rescue. Our observations provide new insights into the mechanisms of the functional and structural relationship of the exo- and endodomain, signal transduction, and receptor genetics, in particular for defective heterozygotes.
* This work was supported by Grants HD-18702 and DK-51469 from the National Institutes of Health.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
¶ To whom correspondence should be addressed: Dept. of Chemistry, University of Kentucky, Lexington, KY 40506-0055. Tel.: 859-257-3163; Fax: 859-257-3229; E-mail: tji@uky.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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Simultaneous Activation of the {delta} Opioid Receptor ({delta}OR)/Sensory Neuron-Specific Receptor-4 (SNSR-4) Hetero-Oligomer by the Mixed Bivalent Agonist Bovine Adrenal Medulla Peptide 22 Activates SNSR-4 but Inhibits {delta}OR Signaling
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Cooperative Conformational Changes in a G-protein-coupled Receptor Dimer, the Leukotriene B4 Receptor BLT1
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Multiple Interactions between Transmembrane Helices Generate the Oligomeric {alpha}1b-Adrenoceptor
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[Abstract] [Full Text] [PDF]
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Hetero-oligomerization between {beta}2- and {beta}3-Adrenergic Receptors Generates a {beta}-Adrenergic Signaling Unit with Distinct Functional Properties
J. Biol. Chem., July 2, 2004; 279(27): 28756 - 28765.
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Trans-Activation of Mutant Follicle-Stimulating Hormone Receptors Selectively Generates Only One of Two Hormone Signals
Mol. Endocrinol., April 1, 2004; 18(4): 968 - 978.
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Misrouted cell surface GnRH receptors as a disease aetiology for congenital isolated hypogonadotrophic hypogonadism
Hum. Reprod. Update, March 1, 2004; 10(2): 177 - 192.
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Constitutive and Agonist-dependent Self-association of the Cell Surface Human Lutropin Receptor
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Dimers of Class A G Protein-coupled Receptors Function via Agonist-mediated Trans-activation of Associated G Proteins
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Dominant-Negative Action of Disease-Causing Gonadotropin-Releasing Hormone Receptor (GnRHR) Mutants: A Trait That Potentially Coevolved with Decreased Plasma Membrane Expression of GnRHR in Humans
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Originally published In Press as doi:10.1074/jbc.M111818200 on February 21, 2002
J. Biol. Chem., Vol. 277, Issue 18, 15795-15800, May 3, 2002
This Article
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Two Defective Heterozygous Luteinizing Hormone Receptors Can Rescue Hormone Action*
ChangWoo LeeDagger , Inhae JiDagger , KiSung RyuDagger , YongSang SongDagger , P. Michael Conn§, and Tae H. JiDagger ¶
From the Dagger Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506-0055 and the § Oregon Regional Primate Research Center and Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, Oregon 97201
Luteinizing hormone receptor is a G protein-coupled receptor and consists of two halves: the N-terminal extracellular half (exodomain) and C-terminal membrane-associated half (endodomain). Hormone binds to the exodomain, and the resulting hormone-exodomain complex modulates the endodomain to generate signals. There are mutations that impair either hormone binding or signal generation. We report that the coexpression of a binding defective mutant and a signal-defective mutant rescues signal generation to produce cAMP. This rescue requires both types of mutant receptors and is dependent on the human chorionic gonadotropin dose, the surface concentration of mutant receptors, and the amino acid position of mutations. Furthermore, random collisions among mutant receptors are not involved in the rescue. Our observations provide new insights into the mechanisms of the functional and structural relationship of the exo- and endodomain, signal transduction, and receptor genetics, in particular for defective heterozygotes.
* This work was supported by Grants HD-18702 and DK-51469 from the National Institutes of Health.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
¶ To whom correspondence should be addressed: Dept. of Chemistry, University of Kentucky, Lexington, KY 40506-0055. Tel.: 859-257-3163; Fax: 859-257-3229; E-mail: tji@uky.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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Home page
Mol. Pharmacol.Home page
A. Breit, K. Gagnidze, L. A. Devi, M. Lagace, and M. Bouvier
Simultaneous Activation of the {delta} Opioid Receptor ({delta}OR)/Sensory Neuron-Specific Receptor-4 (SNSR-4) Hetero-Oligomer by the Mixed Bivalent Agonist Bovine Adrenal Medulla Peptide 22 Activates SNSR-4 but Inhibits {delta}OR Signaling
Mol. Pharmacol., August 1, 2006; 70(2): 686 - 696.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
G. Pascal and G. Milligan
Functional Complementation and the Analysis of Opioid Receptor Homodimerization
Mol. Pharmacol., September 1, 2005; 68(3): 905 - 915.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
D. Mesnier and J.-L. Baneres
Cooperative Conformational Changes in a G-protein-coupled Receptor Dimer, the Leukotriene B4 Receptor BLT1
J. Biol. Chem., November 26, 2004; 279(48): 49664 - 49670.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
J. J. Carrillo, J. F. Lopez-Gimenez, and G. Milligan
Multiple Interactions between Transmembrane Helices Generate the Oligomeric {alpha}1b-Adrenoceptor
Mol. Pharmacol., November 1, 2004; 66(5): 1123 - 1137.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
A. Breit, M. Lagace, and M. Bouvier
Hetero-oligomerization between {beta}2- and {beta}3-Adrenergic Receptors Generates a {beta}-Adrenergic Signaling Unit with Distinct Functional Properties
J. Biol. Chem., July 2, 2004; 279(27): 28756 - 28765.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
G. Milligan
G Protein-Coupled Receptor Dimerization: Function and Ligand Pharmacology
Mol. Pharmacol., July 1, 2004; 66(1): 1 - 7.
[Abstract] [Full Text] [PDF]
Home page
Mol. Endocrinol.Home page
I. Ji, C. Lee, M. Jeoung, Y. Koo, G. A. Sievert, and T. H. Ji
Trans-Activation of Mutant Follicle-Stimulating Hormone Receptors Selectively Generates Only One of Two Hormone Signals
Mol. Endocrinol., April 1, 2004; 18(4): 968 - 978.
[Abstract] [Full Text] [PDF]
Home page
Hum Reprod UpdateHome page
A. Ulloa-Aguirre, J. A. Janovick, A. Leanos-Miranda, and P. M. Conn
Misrouted cell surface GnRH receptors as a disease aetiology for congenital isolated hypogonadotrophic hypogonadism
Hum. Reprod. Update, March 1, 2004; 10(2): 177 - 192.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
Y.-X. Tao, N. B. Johnson, and D. L. Segaloff
Constitutive and Agonist-dependent Self-association of the Cell Surface Human Lutropin Receptor
J. Biol. Chem., February 13, 2004; 279(7): 5904 - 5914.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
J. J. Carrillo, J. Pediani, and G. Milligan
Dimers of Class A G Protein-coupled Receptors Function via Agonist-mediated Trans-activation of Associated G Proteins
J. Biol. Chem., October 24, 2003; 278(43): 42578 - 42587.
[Abstract] [Full Text] [PDF]
Home page
J. Clin. Endocrinol. Metab.Home page
A. Leanos-Miranda, A. Ulloa-Aguirre, T. H. Ji, J. A. Janovick, and P. M. Conn
Dominant-Negative Action of Disease-Causing Gonadotropin-Releasing Hormone Receptor (GnRHR) Mutants: A Trait That Potentially Coevolved with Decreased Plasma Membrane Expression of GnRHR in Humans
J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3360 - 3367.
[Abstract] [Full Text] [PDF]
Home page
Mol. Endocrinol.Home page
P. Narayan, J. Gray, and D. Puett
Yoked Complexes of Human Choriogonadotropin and the Lutropin Receptor: Evidence that Monomeric Individual Subunits Are Inactive
Mol. Endocrinol., December 1, 2002; 16(12): 2733 - 2745.
[Abstract] [Full Text] [PDF]
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
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Originally published In Press as doi:10.1074/jbc.M111818200 on February 21, 2002
J. Biol. Chem., Vol. 277, Issue 18, 15795-15800, May 3, 2002
This Article
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What's this?
Two Defective Heterozygous Luteinizing Hormone Receptors Can Rescue Hormone Action*
ChangWoo LeeDagger , Inhae JiDagger , KiSung RyuDagger , YongSang SongDagger , P. Michael Conn§, and Tae H. JiDagger ¶
From the Dagger Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506-0055 and the § Oregon Regional Primate Research Center and Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, Oregon 97201
Luteinizing hormone receptor is a G protein-coupled receptor and consists of two halves: the N-terminal extracellular half (exodomain) and C-terminal membrane-associated half (endodomain). Hormone binds to the exodomain, and the resulting hormone-exodomain complex modulates the endodomain to generate signals. There are mutations that impair either hormone binding or signal generation. We report that the coexpression of a binding defective mutant and a signal-defective mutant rescues signal generation to produce cAMP. This rescue requires both types of mutant receptors and is dependent on the human chorionic gonadotropin dose, the surface concentration of mutant receptors, and the amino acid position of mutations. Furthermore, random collisions among mutant receptors are not involved in the rescue. Our observations provide new insights into the mechanisms of the functional and structural relationship of the exo- and endodomain, signal transduction, and receptor genetics, in particular for defective heterozygotes.
* This work was supported by Grants HD-18702 and DK-51469 from the National Institutes of Health.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
¶ To whom correspondence should be addressed: Dept. of Chemistry, University of Kentucky, Lexington, KY 40506-0055. Tel.: 859-257-3163; Fax: 859-257-3229; E-mail: tji@uky.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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This article has been cited by other articles:
Home page
Mol. Pharmacol.Home page
A. Breit, K. Gagnidze, L. A. Devi, M. Lagace, and M. Bouvier
Simultaneous Activation of the {delta} Opioid Receptor ({delta}OR)/Sensory Neuron-Specific Receptor-4 (SNSR-4) Hetero-Oligomer by the Mixed Bivalent Agonist Bovine Adrenal Medulla Peptide 22 Activates SNSR-4 but Inhibits {delta}OR Signaling
Mol. Pharmacol., August 1, 2006; 70(2): 686 - 696.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
G. Pascal and G. Milligan
Functional Complementation and the Analysis of Opioid Receptor Homodimerization
Mol. Pharmacol., September 1, 2005; 68(3): 905 - 915.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
D. Mesnier and J.-L. Baneres
Cooperative Conformational Changes in a G-protein-coupled Receptor Dimer, the Leukotriene B4 Receptor BLT1
J. Biol. Chem., November 26, 2004; 279(48): 49664 - 49670.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
J. J. Carrillo, J. F. Lopez-Gimenez, and G. Milligan
Multiple Interactions between Transmembrane Helices Generate the Oligomeric {alpha}1b-Adrenoceptor
Mol. Pharmacol., November 1, 2004; 66(5): 1123 - 1137.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
A. Breit, M. Lagace, and M. Bouvier
Hetero-oligomerization between {beta}2- and {beta}3-Adrenergic Receptors Generates a {beta}-Adrenergic Signaling Unit with Distinct Functional Properties
J. Biol. Chem., July 2, 2004; 279(27): 28756 - 28765.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
G. Milligan
G Protein-Coupled Receptor Dimerization: Function and Ligand Pharmacology
Mol. Pharmacol., July 1, 2004; 66(1): 1 - 7.
[Abstract] [Full Text] [PDF]
Home page
Mol. Endocrinol.Home page
I. Ji, C. Lee, M. Jeoung, Y. Koo, G. A. Sievert, and T. H. Ji
Trans-Activation of Mutant Follicle-Stimulating Hormone Receptors Selectively Generates Only One of Two Hormone Signals
Mol. Endocrinol., April 1, 2004; 18(4): 968 - 978.
[Abstract] [Full Text] [PDF]
Home page
Hum Reprod UpdateHome page
A. Ulloa-Aguirre, J. A. Janovick, A. Leanos-Miranda, and P. M. Conn
Misrouted cell surface GnRH receptors as a disease aetiology for congenital isolated hypogonadotrophic hypogonadism
Hum. Reprod. Update, March 1, 2004; 10(2): 177 - 192.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
Y.-X. Tao, N. B. Johnson, and D. L. Segaloff
Constitutive and Agonist-dependent Self-association of the Cell Surface Human Lutropin Receptor
J. Biol. Chem., February 13, 2004; 279(7): 5904 - 5914.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
J. J. Carrillo, J. Pediani, and G. Milligan
Dimers of Class A G Protein-coupled Receptors Function via Agonist-mediated Trans-activation of Associated G Proteins
J. Biol. Chem., October 24, 2003; 278(43): 42578 - 42587.
[Abstract] [Full Text] [PDF]
Home page
J. Clin. Endocrinol. Metab.Home page
A. Leanos-Miranda, A. Ulloa-Aguirre, T. H. Ji, J. A. Janovick, and P. M. Conn
Dominant-Negative Action of Disease-Causing Gonadotropin-Releasing Hormone Receptor (GnRHR) Mutants: A Trait That Potentially Coevolved with Decreased Plasma Membrane Expression of GnRHR in Humans
J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3360 - 3367.
[Abstract] [Full Text] [PDF]
Home page
Mol. Endocrinol.Home page
P. Narayan, J. Gray, and D. Puett
Yoked Complexes of Human Choriogonadotropin and the Lutropin Receptor: Evidence that Monomeric Individual Subunits Are Inactive
Mol. Endocrinol., December 1, 2002; 16(12): 2733 - 2745.
[Abstract] [Full Text] [PDF]
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
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JBC Avanti Polar Lipids
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Originally published In Press as doi:10.1074/jbc.M111818200 on February 21, 2002
J. Biol. Chem., Vol. 277, Issue 18, 15795-15800, May 3, 2002
This Article
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What's this?
Two Defective Heterozygous Luteinizing Hormone Receptors Can Rescue Hormone Action*
ChangWoo LeeDagger , Inhae JiDagger , KiSung RyuDagger , YongSang SongDagger , P. Michael Conn§, and Tae H. JiDagger ¶
From the Dagger Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506-0055 and the § Oregon Regional Primate Research Center and Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, Oregon 97201
Luteinizing hormone receptor is a G protein-coupled receptor and consists of two halves: the N-terminal extracellular half (exodomain) and C-terminal membrane-associated half (endodomain). Hormone binds to the exodomain, and the resulting hormone-exodomain complex modulates the endodomain to generate signals. There are mutations that impair either hormone binding or signal generation. We report that the coexpression of a binding defective mutant and a signal-defective mutant rescues signal generation to produce cAMP. This rescue requires both types of mutant receptors and is dependent on the human chorionic gonadotropin dose, the surface concentration of mutant receptors, and the amino acid position of mutations. Furthermore, random collisions among mutant receptors are not involved in the rescue. Our observations provide new insights into the mechanisms of the functional and structural relationship of the exo- and endodomain, signal transduction, and receptor genetics, in particular for defective heterozygotes.
* This work was supported by Grants HD-18702 and DK-51469 from the National Institutes of Health.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
¶ To whom correspondence should be addressed: Dept. of Chemistry, University of Kentucky, Lexington, KY 40506-0055. Tel.: 859-257-3163; Fax: 859-257-3229; E-mail: tji@uky.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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This article has been cited by other articles:
Home page
Mol. Pharmacol.Home page
A. Breit, K. Gagnidze, L. A. Devi, M. Lagace, and M. Bouvier
Simultaneous Activation of the {delta} Opioid Receptor ({delta}OR)/Sensory Neuron-Specific Receptor-4 (SNSR-4) Hetero-Oligomer by the Mixed Bivalent Agonist Bovine Adrenal Medulla Peptide 22 Activates SNSR-4 but Inhibits {delta}OR Signaling
Mol. Pharmacol., August 1, 2006; 70(2): 686 - 696.
[Abstract] [Full Text] [PDF]
Home page
Mol. Pharmacol.Home page
G. Pascal and G. Milligan
Functional Complementation and the Analysis of Opioid Receptor Homodimerization
Mol. Pharmacol., September 1, 2005; 68(3): 905 - 915.
[Abstract] [Full Text] [PDF]
Home page
J. Biol. Chem.Home page
D. Mesnier and J.-L. Baneres
Cooperative Conformational Changes in a G-protein-coupled Receptor Dimer, the Leukotriene B4 Receptor BLT1
J. Biol. Chem., November 26, 2004; 279(48): 49664 - 49670.
[Abstract] [Full Text] [PDF]
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Mol. Pharmacol.Home page
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Trans-Activation of Mutant Follicle-Stimulating Hormone Receptors Selectively Generates Only One of Two Hormone Signals
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Hum Reprod UpdateHome page
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Y.-X. Tao, N. B. Johnson, and D. L. Segaloff
Constitutive and Agonist-dependent Self-association of the Cell Surface Human Lutropin Receptor
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Dimers of Class A G Protein-coupled Receptors Function via Agonist-mediated Trans-activation of Associated G Proteins
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Originally published In Press as doi:10.1074/jbc.M111818200 on February 21, 2002
J. Biol. Chem., Vol. 277, Issue 18, 15795-15800, May 3, 2002
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Two Defective Heterozygous Luteinizing Hormone Receptors Can Rescue Hormone Action*
ChangWoo LeeDagger , Inhae JiDagger , KiSung RyuDagger , YongSang SongDagger , P. Michael Conn§, and Tae H. JiDagger ¶
From the Dagger Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506-0055 and the § Oregon Regional Primate Research Center and Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, Oregon 97201
Luteinizing hormone receptor is a G protein-coupled receptor and consists of two halves: the N-terminal extracellular half (exodomain) and C-terminal membrane-associated half (endodomain). Hormone binds to the exodomain, and the resulting hormone-exodomain complex modulates the endodomain to generate signals. There are mutations that impair either hormone binding or signal generation. We report that the coexpression of a binding defective mutant and a signal-defective mutant rescues signal generation to produce cAMP. This rescue requires both types of mutant receptors and is dependent on the human chorionic gonadotropin dose, the surface concentration of mutant receptors, and the amino acid position of mutations. Furthermore, random collisions among mutant receptors are not involved in the rescue. Our observations provide new insights into the mechanisms of the functional and structural relationship of the exo- and endodomain, signal transduction, and receptor genetics, in particular for defective heterozygotes.
* This work was supported by Grants HD-18702 and DK-51469 from the National Institutes of Health.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
¶ To whom correspondence should be addressed: Dept. of Chemistry, University of Kentucky, Lexington, KY 40506-0055. Tel.: 859-257-3163; Fax: 859-257-3229; E-mail: tji@uky.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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Hetero-oligomerization between {beta}2- and {beta}3-Adrenergic Receptors Generates a {beta}-Adrenergic Signaling Unit with Distinct Functional Properties
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Trans-Activation of Mutant Follicle-Stimulating Hormone Receptors Selectively Generates Only One of Two Hormone Signals
Mol. Endocrinol., April 1, 2004; 18(4): 968 - 978.
[Abstract] [Full Text] [PDF]
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Misrouted cell surface GnRH receptors as a disease aetiology for congenital isolated hypogonadotrophic hypogonadism
Hum. Reprod. Update, March 1, 2004; 10(2): 177 - 192.
[Abstract] [Full Text] [PDF]
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Constitutive and Agonist-dependent Self-association of the Cell Surface Human Lutropin Receptor
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[Abstract] [Full Text] [PDF]
Home page
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Dimers of Class A G Protein-coupled Receptors Function via Agonist-mediated Trans-activation of Associated G Proteins
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Dominant-Negative Action of Disease-Causing Gonadotropin-Releasing Hormone Receptor (GnRHR) Mutants: A Trait That Potentially Coevolved with Decreased Plasma Membrane Expression of GnRHR in Humans
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Yoked Complexes of Human Choriogonadotropin and the Lutropin Receptor: Evidence that Monomeric Individual Subunits Are Inactive
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[Abstract] [Full Text] [PDF]
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Capítulo
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Edição
* Almeida Corrigida e Revisada Fiel (Ed. 1994)Almeida Revisada Imprensa Bíblica (Ed. 1967)Almeida Revista e Atualizada (Ed. 1993)Almeida Revista e Corrigida (1969) (Ed. 1969)Almeida Revista e Corrigida (1995) (Ed. 1995)Sociedade Bíblica BritânicaVersão CatólicaAmerican Standard Version (Ed. 1901)Basic English (Ed. 1965)Darby, John Nelson (Ed. 1890)King JamesWebster (Ed. 1833)Young's Literal (Ed. 1862)Reina Valera (Ed. 1960)La Bible de l'Épée (Ed. 2005)Louis Segond (Ed. 1910)Martin (Ed. 1744)Ostervald (Ed. 1996)Afrikaans (Ed. 1953)Arabic - Smith / Van Dyke (Ed. 1865)Czech BKRCzech CEPDanishElberfelder (Ed. 1905)Elberfelder (Ed. 1871)Luther (Ed. 1912)Luther (Ed. 1545)Schlachter (Ed. 1951)Textus Receptus (Ed. 1894)Westcott/Hort, UBS4 variants (Ed. 1881)Esperanto (Ed. 1926)EstonianFinnish Bible (Ed. 1776)Pyhä Raamattu (Ed. 1992)Pyhä Raamattu (Ed. 1938)Aleppo Codex (Ed. 920)Westminster Leningrad Codex (Ed. 1008)Károli (Ed. 1908)Giovanni Diodati (Ed. 1649)Riveduta (Ed. 1927)KoreanLithuanianMaoriMyanmar/Burmse - Judson (Ed. 1835)DutchDet Norsk Bibelselskap (Ed. 1930)Cornilescu (Ed. 1921)Синодальный перевод (Synodal) (Ed. 1876)Swedish (Ed. 1917)Türkçe (Ed. 2002)Tiếng Việt (Ed. 1934)isiXhosa (Ed. 1996)Chinese Union Version (Simplified)Chinese Union Version (Traditional)New Chinese Version (Simplified) (Ed. 1992)New Chinese Version (Traditional) (Ed. 1992)
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* Almeida Corrigida e Revisada Fiel (Ed. 1994)Almeida Revisada Imprensa Bíblica (Ed. 1967)Almeida Revista e Atualizada (Ed. 1993)Almeida Revista e Corrigida (1969) (Ed. 1969)Almeida Revista e Corrigida (1995) (Ed. 1995)Sociedade Bíblica BritânicaVersão CatólicaAmerican Standard Version (Ed. 1901)Basic English (Ed. 1965)Darby, John Nelson (Ed. 1890)King JamesWebster (Ed. 1833)Young's Literal (Ed. 1862)Reina Valera (Ed. 1960)La Bible de l'Épée (Ed. 2005)Louis Segond (Ed. 1910)Martin (Ed. 1744)Ostervald (Ed. 1996)Afrikaans (Ed. 1953)Arabic - Smith / Van Dyke (Ed. 1865)Czech BKRCzech CEPDanishElberfelder (Ed. 1905)Elberfelder (Ed. 1871)Luther (Ed. 1912)Luther (Ed. 1545)Schlachter (Ed. 1951)Textus Receptus (Ed. 1894)Westcott/Hort, UBS4 variants (Ed. 1881)Esperanto (Ed. 1926)EstonianFinnish Bible (Ed. 1776)Pyhä Raamattu (Ed. 1992)Pyhä Raamattu (Ed. 1938)Aleppo Codex (Ed. 920)Westminster Leningrad Codex (Ed. 1008)Károli (Ed. 1908)Giovanni Diodati (Ed. 1649)Riveduta (Ed. 1927)KoreanLithuanianMaoriMyanmar/Burmse - Judson (Ed. 1835)DutchDet Norsk Bibelselskap (Ed. 1930)Cornilescu (Ed. 1921)Синодальный перевод (Synodal) (Ed. 1876)Swedish (Ed. 1917)Türkçe (Ed. 2002)Tiếng Việt (Ed. 1934)isiXhosa (Ed. 1996)Chinese Union Version (Simplified)Chinese Union Version (Traditional)New Chinese Version (Simplified) (Ed. 1992)New Chinese Version (Traditional) (Ed. 1992)
* Anterior
* Próximo
Deuteronômio 1
1 mapa ¶ Estas são as palavras que Moisés falou a todo o Israel além do Jordão, no deserto, na planície defronte do Mar Vermelho, entre Parã e Tófel, e Labã, e Hazerote, e Di-Zaabe.
2 mapa Onze jornadas há desde Horebe, caminho do monte Seir, até Cades-Barnéia.
3 E sucedeu que, no ano quadragésimo, no mês undécimo, no primeiro dia do mês, Moisés falou aos filhos de Israel, conforme a tudo o que o SENHOR lhe mandara acerca deles.
4 mapa Depois que feriu a Siom, rei dos amorreus, que habitava em Hesbom, e a Ogue, rei de Basã, que habitava em Astarote, em Edrei.
5 mapa Além do Jordão, na terra de Moabe, começou Moisés a declarar esta lei, dizendo:
6 mapa O SENHOR nosso Deus nos falou em Horebe, dizendo: Assaz vos haveis demorado neste monte.
7 mapa Voltai-vos, e parti, e ide à montanha dos amorreus, e a todos os seus vizinhos, à planície, e à montanha, e ao vale, e ao sul, e à margem do mar; à terra dos cananeus, e ao Líbano, até ao grande rio, o rio Eufrates.
8 Eis que tenho posto esta terra diante de vós; entrai e possuí a terra que o SENHOR jurou a vossos pais, Abraão, Isaque e Jacó, que a daria a eles e à sua descendência depois deles.
9 ¶ E no mesmo tempo eu vos falei, dizendo: Eu sozinho não poderei levar-vos.
10 O SENHOR vosso Deus já vos tem multiplicado; e eis que em multidão sois hoje como as estrelas do céu.
11 O SENHOR Deus de vossos pais vos aumente, ainda mil vezes mais do que sois; e vos abençoe, como vos tem falado.
12 Como suportaria eu sozinho os vossos fardos, e as vossas cargas, e as vossas contendas?
13 Tomai-vos homens sábios e entendidos, experimentados entre as vossas tribos, para que os ponha por chefes sobre vós.
14 Então vós me respondestes, e dissestes: Bom é fazer o que tens falado.
15 Tomei, pois, os chefes de vossas tribos, homens sábios e experimentados, e os tenho posto por cabeças sobre vós, por capitães de milhares, e por capitães de cem, e por capitães de cinqüenta, e por capitães de dez, e por governadores das vossas tribos.
16 E no mesmo tempo mandei a vossos juízes, dizendo: Ouvi a causa entre vossos irmãos, e julgai justamente entre o homem e seu irmão, e entre o estrangeiro que está com ele.
17 Não discriminareis as pessoas em juízo; ouvireis assim o pequeno como o grande; não temereis a face de ninguém, porque o juízo é de Deus; porém a causa que vos for difícil fareis vir a mim, e eu a ouvirei.
18 Assim naquele tempo vos ordenei todas as coisas que havíeis de fazer.
19 mapa ¶ Então partimos de Horebe, e caminhamos por todo aquele grande e tremendo deserto que vistes, pelo caminho das montanhas dos amorreus, como o SENHOR nosso Deus nos ordenara; e chegamos a Cades-Barnéia.
20 Então eu vos disse: Chegados sois às montanhas dos amorreus, que o SENHOR nosso Deus nos dá.
21 Eis aqui o SENHOR teu Deus tem posto esta terra diante de ti; sobe, toma posse dela, como te falou o SENHOR Deus de teus pais; não temas, e não te assustes.
22 Então todos vós chegastes a mim, e dissestes: Mandemos homens adiante de nós, para que nos espiem a terra e, de volta, nos ensinem o caminho pelo qual devemos subir, e as cidades a que devemos ir.
23 Isto me pareceu bem; de modo que de vós tomei doze homens, de cada tribo um homem.
24 mapa E foram-se, e subiram à montanha, e chegaram até ao vale de Escol, e o espiaram.
25 E tomaram do fruto da terra nas suas mãos, e no-lo trouxeram e nos informaram, dizendo: Boa é a terra que nos dá o SENHOR nosso Deus.
26 Porém vós não quisestes subir; mas fostes rebeldes ao mandado do SENHOR nosso Deus.
27 mapa E murmurastes nas vossas tendas, e dissestes: Porquanto o SENHOR nos odeia, nos tirou da terra do Egito para nos entregar nas mãos dos amorreus, para destruir-nos.
28 Para onde subiremos? Nossos irmãos fizeram com que se derretesse o nosso coração, dizendo: Maior e mais alto é este povo do que nós, as cidades são grandes e fortificadas até aos céus; e também vimos ali filhos dos gigantes.
29 Então eu vos disse: Não vos espanteis, nem os temais.
30 mapa O SENHOR vosso Deus que vai adiante de vós, ele pelejará por vós, conforme a tudo o que fez convosco, diante de vossos olhos, no Egito;
31 Como também no deserto, onde vistes que o SENHOR vosso Deus nele vos levou, como um homem leva seu filho, por todo o caminho que andastes, até chegardes a este lugar.
32 Mas nem por isso crestes no SENHOR vosso Deus,
33 Que foi adiante de vós por todo o caminho, para vos achar o lugar onde vós deveríeis acampar; de noite no fogo, para vos mostrar o caminho por onde havíeis de andar, e de dia na nuvem.
34 Ouvindo, pois, o SENHOR a voz das vossas palavras, indignou-se, e jurou, dizendo:
35 Nenhum dos homens desta maligna geração verá esta boa terra que jurei dar a vossos pais.
36 Salvo Calebe, filho de Jefoné; ele a verá, e a terra que pisou darei a ele e a seus filhos; porquanto perseverou em seguir ao SENHOR.
37 Também o SENHOR se indignou contra mim por causa de vós, dizendo: Também tu lá não entrarás.
38 Josué, filho de Num, que está diante de ti, ele ali entrará; fortalece-o, porque ele a fará herdar a Israel.
39 E vossos meninos, de quem dissestes: Por presa serão; e vossos filhos, que hoje não conhecem nem o bem nem o mal, eles ali entrarão, e a eles a darei, e eles a possuirão.
40 mapa Porém vós virai-vos, e parti para o deserto, pelo caminho do Mar Vermelho.
41 Então respondestes, e me dissestes: Pecamos contra o SENHOR; nós subiremos e pelejaremos, conforme a tudo o que nos ordenou o SENHOR nosso Deus. E armastes-vos, cada um de vós, dos seus instrumentos de guerra, e estivestes prestes para subir à montanha.
42 E disse-me o SENHOR: Dize-lhes: Não subais nem pelejeis, pois não estou no meio de vós; para que não sejais feridos diante de vossos inimigos.
43 Porém, falando-vos eu, não ouvistes; antes fostes rebeldes ao mandado do SENHOR, e vos ensoberbecestes, e subistes à montanha.
44 mapa E os amorreus, que habitavam naquela montanha, vos saíram ao encontro; e perseguiram-vos como fazem as abelhas e vos derrotaram desde Seir até Horma.
45 Tornando, pois, vós, e chorando perante o SENHOR, o SENHOR não ouviu a vossa voz, nem vos escutou.
46 mapa Assim permanecestes muitos dias em Cades, pois ali vos demorastes muito.
Vulgate (Latin): Leviticus Chapter 6
1 Locutus est Dominus ad Moysen, dicens:
2 Anima quæ peccaverit, et contempto Domino, negaverit proximo suo depositum quod fidei ejus creditum fuerat, vel vi aliquid extorserit, aut calumniam fecerit,
3 sive rem perditam invenerit, et inficians insuper pejeraverit, et quodlibet aliud ex pluribus fecerit, in quibus solent peccare homines,
4 convicta delicti,
5 reddet omnia, quæ per fraudem voluit obtinere, integra, et quintam insuper partem domino cui damnum intulerat.
6 Pro peccato autem suo offeret arietem immaculatum de grege, et dabit eum sacerdoti, juxta æstimationem mensuramque delicti:
7 qui rogabit pro eo coram Domino, et dimittetur illi pro singulis quæ faciendo peccavit.
8 Locutusque est Dominus ad Moysen, dicens:
9 Præcipe Aaron et filiis ejus: Hæc est lex holocausti: cremabitur in altari tota nocte usque mane: ignis ex eodem altari erit.
10 Vestietur tunica sacerdos et feminalibus lineis: tolletque cineres, quos vorans ignis exussit, et ponens juxta altare,
11 spoliabitur prioribus vestimentis, indutusque aliis, efferret eos extra castra, et in loco mundissimo usque ad favillam consumi faciet.
12 Ignis autem in altari semper ardebit, quem nutriet sacerdos subjiciens ligna mane per singulos dies, et imposito holocausto, desuper adolebit adipes pacificorum.
13 Ignis est iste perpetuus, qui numquam deficiet in altari.
14 Hæc est lex sacrificii et libamentorum, quæ offerent filii Aaron coram Domino, et coram altari.
15 Tollet sacerdos pugillum similæ, quæ conspersa est oleo, et totum thus, quod super similam positum est: adolebitque illud in altari in monimentum odoris suavissimi Domino:
16 reliquam autem partem similæ comedet Aaron cum filiis suis, absque fermento: et comedet in loco sancto atrii tabernaculi.
17 Ideo autem non fermentabitur, quia pars ejus in Domini offertur incensum. Sanctum sanctorum erit, sicut pro peccato atque delicto.
18 Mares tantum stirpis Aaron comedent illud. Legitimum ac sempiternum erit in generationibus vestris de sacrificiis Domini: omnis qui tetigerit illa, sanctificabitur.
19 Locutusque est Dominus ad Moysen, dicens:
20 Hæc est oblatio Aaron, et filiorum ejus, quam offerre debent Domino in die unctionis suæ. Decimam partem ephi offerent similæ in sacrificio sempiterno, medium ejus mane, et medium ejus vespere:
21 quæ in sartagine oleo conspersa frigetur. Offeret autem eam calidam in odorem suavissimum Domino
22 sacerdos, qui jure patri successerit, et tota cremabitur in altari.
23 Omne enim sacrificium sacerdotum igne consumetur, nec quisquam comedet ex eo.
24 Locutus est autem Dominus ad Moysen, dicens:
25 Loquere Aaron et filiis ejus: Ista est lex hostiæ pro peccato: in loco ubi offertur holocaustum, immolabitur coram Domino. Sanctum sanctorum est.
26 Sacerdos, qui offert, comedet eam in loco sancto, in atrio tabernaculi.
27 Quidquid tetigerit carnes ejus, sanctificabitur. Si de sanguine illius vestis fuerit aspersa, lavabitur in loco sancto.
28 Vas autem fictile, in quo cocta est, confringetur; quod si vas æneum fuerit, defricabitur, et lavabitur aqua.
29 Omnis masculus de genere sacerdotali vescetur de carnibus ejus, quia Sanctum sanctorum est.
30 Hostia enim quæ cæditur pro peccato, cujus sanguis infertur in tabernaculum testimonii ad expiandum in sanctuario, non comedetur, sed comburetur igni.
Este texto de AdaS eleva-nos a novos níveis de paroxismo e cataliza, pode-se afirmar, uma nova visão da Realidade. Vemos agora, quebrados os liames da linguagem e libertos de superfluos alter egos, que deus, afinal provavelmente não existe, que fodemos menos do que devíamos e que basicamemte andámos a desperdiçar a nossa vida, preocupendo-nos com quimeras por nós reificadas. Sonhos da Razão, monstros que nos atormentaram demasiado tempo. Agasalhemos pois nossas magras morcelas, com a tusa, que se esmaece na meia-idade e assumamos que somos uma trupe de coirões nihilistas, infantis e inconsequentes. Atafulhemos enchidos, fruta, legumes e frutos-do-mar em nossas tripas cagueiras onde já palpita o germe do pólipo maligno que nos levará á tumba após uma longa e desnecessária quimioterapia.
tás maluco.
el sueño de la razón produce mosntruos, eso ya lo vió Goya , não es nada nuevo
libre de la inteligencia el ser humano puede ser terrible
afortunadamente tu no estas en ese intevalo
;-)
Faço minhas as palavras da Luí.
Ainda que as diga e escreva em português...
Raisparta isto!
Oh!
Oh2!
...clonito disse:
...fala por ti jarreta mijador de xanatos!
...clonito rompe-esfíncteres disse:
...Tomai e ouvi todos, esta oferenda de Natal...outra opção era um balde de merda:
http://www.glitter-graphics.com/videos/details.php?video_id=XiSSkPHpzP8&title=The+Exploited+--+The+Mod+Song
A merda é humana, de cão, de pombo ou de cavalo?
O balde é de zinco, de plástico rasca ou de plástico de boa qualidade?
Na hipótese de ser um balde de zinco com merda de cavalo, aceito a oferta e as minhas plantas agradecerão.
Qualquer outra hipótese será, mesmo assim, de considerar como razoavelmente boa alternativa a ter de ouvir Exploited.
Concordo inteiramente.
E subscrevo.
aqui ta chover ,o juro pela ostia bendita
estou a ouvir na radio a um gajo que fala português com sotaque argentino- lunfardo
e dice "supoño" e "acho" pero assim: com ñ e nao com nh ,e com ch e nao com sssh
e diz pOrtugues e não pUrtuguês com uma O redonda e muito aberta
argg
e dice falo como si dijese po***
... la ostia, tu!
Que se passa hoje aqui?
A falta de comparência dos comensais habituais é por ser feriado, dia da Imaculada (cof, cof, cof) Conceição??
Só a lui aqui vem , é?
A-ha!
Bock fugaz!
A Nossa Senhora Imaculada Conceição é, imagine-se, padroeira de Portugal. Nem mais!
Vivó luxo!
Espanha tem de se contentar com santos da 2ª divisão. Toma!
São Tiago e Santa Teresa d’Ávila? Pfffff!
Felizmente o rei D. João IV, poucos anos após a Restauração e só pra chatear os espanhóis, decidiu não entregar o pelouro da nossa protecção a santos menores.
Como, por exemplo, São Cristóvão, padroeiro do pessoal que viaja em pé nos transportes públicos ou, pior ainda, Santa Apolónia, a padroeira daquelas pessoas que viajam no telhado dos comboios na India.
Claro que, se nós fossemos gente interesseira e gananciosa, o D.João IV tinha escolhido o Santo Olavo, que agora é padroeiro da Noruega, São Gall padroeiro da Suiça ou São Lucio, padroeiro das offshores em geral e do do Liechtenstein em particular, mas, graças a Deus, somos honrados, humildes e orgulhosos dos nossos pés rapados.
Por isso, oremos ao Santo Olavo e aos seus compinchas Lucio e Gall, dizendo-lhes, com arrogância de carocho, para meterem o bem-estar, os altos índices de desenvolvimento e todo aquele dinheiro no cu.
Amen!
uam data de beatos , isso é que são vocês e papaostias.
Papem-me!!!!
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