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激素松弛素对孤儿受体的激活作用。

Activation of orphan receptors by the hormone relaxin.

作者信息

Hsu Sheau Yu, Nakabayashi Koji, Nishi Shinya, Kumagai Jin, Kudo Masataka, Sherwood O David, Hsueh Aaron J W

机构信息

Division of Reproductive Biology, Department of Gynecology and Obstetrics, Stanford University School of Medicine, Stanford, CA 94305, USA.

出版信息

Science. 2002 Jan 25;295(5555):671-4. doi: 10.1126/science.1065654.

DOI:10.1126/science.1065654
PMID:11809971
Abstract

Relaxin is a hormone important for the growth and remodeling of reproductive and other tissues during pregnancy. Although binding sites for relaxin are widely distributed, the nature of its receptor has been elusive. Here, we demonstrate that two orphan heterotrimeric guanine nucleotide binding protein (G protein)-coupled receptors, LGR7 and LGR8, are capable of mediating the action of relaxin through an adenosine 3',5'-monophosphate (cAMP)-dependent pathway distinct from that of the structurally related insulin and insulin-like growth factor family ligand. Treatment of antepartum mice with the soluble ligand-binding region of LGR7 caused parturition delay. The wide and divergent distribution of the two relaxin receptors implicates their roles in reproductive, brain, renal, cardiovascular, and other functions.

摘要

松弛素是一种在孕期对生殖及其他组织的生长和重塑很重要的激素。尽管松弛素的结合位点广泛分布,但其受体的性质一直难以捉摸。在此,我们证明了两个孤儿异源三聚体鸟嘌呤核苷酸结合蛋白(G蛋白)偶联受体,LGR7和LGR8,能够通过一条与结构相关的胰岛素和胰岛素样生长因子家族配体不同的3',5'-环磷酸腺苷(cAMP)依赖性途径介导松弛素的作用。用LGR7的可溶性配体结合区域处理产前小鼠会导致分娩延迟。两种松弛素受体广泛且不同的分布表明它们在生殖、大脑、肾脏、心血管及其他功能中发挥作用。

相似文献

1
Activation of orphan receptors by the hormone relaxin.激素松弛素对孤儿受体的激活作用。
Science. 2002 Jan 25;295(5555):671-4. doi: 10.1126/science.1065654.
2
Relaxin-3, INSL5, and their receptors.松弛素-3、胰岛素样肽5及其受体。
Results Probl Cell Differ. 2008;46:213-37. doi: 10.1007/400_2007_055.
3
Multiple binding sites revealed by interaction of relaxin family peptides with native and chimeric relaxin family peptide receptors 1 and 2 (LGR7 and LGR8).松弛素家族肽与天然及嵌合型松弛素家族肽受体1和2(LGR7和LGR8)相互作用所揭示的多个结合位点。
J Pharmacol Exp Ther. 2005 May;313(2):677-87. doi: 10.1124/jpet.104.080655. Epub 2005 Jan 12.
4
Identification and characterization of the mouse and rat relaxin receptors as the novel orthologues of human leucine-rich repeat-containing G-protein-coupled receptor 7.小鼠和大鼠松弛素受体作为富含亮氨酸重复序列的人G蛋白偶联受体7的新型直系同源物的鉴定与表征。
Clin Exp Pharmacol Physiol. 2004 Nov;31(11):828-32. doi: 10.1111/j.1440-1681.2004.04075.x.
5
Relaxin family peptide receptors RXFP1 and RXFP2 modulate cAMP signaling by distinct mechanisms.松弛素家族肽受体RXFP1和RXFP2通过不同机制调节环磷酸腺苷(cAMP)信号传导。
Mol Pharmacol. 2006 Jul;70(1):214-26. doi: 10.1124/mol.105.021691. Epub 2006 Mar 28.
6
Endocrinology. This hormone has been relaxin' too long!
Science. 2002 Jan 25;295(5555):637-8. doi: 10.1126/science.1069234.
7
International Union of Pharmacology LVII: recommendations for the nomenclature of receptors for relaxin family peptides.国际药理学联合会LVII:松弛素家族肽受体命名法建议
Pharmacol Rev. 2006 Mar;58(1):7-31. doi: 10.1124/pr.58.1.9.
8
Identification of binding sites with differing affinity and potency for relaxin analogues on LGR7 and LGR8 receptors.鉴定松弛素类似物在LGR7和LGR8受体上具有不同亲和力和效力的结合位点。
Ann N Y Acad Sci. 2005 May;1041:17-21. doi: 10.1196/annals.1282.004.
9
Roles of the receptor, the ligand, and the cell in the signal transduction pathways utilized by the relaxin family peptide receptors 1-3.受体、配体和细胞在松弛素家族肽受体1-3所利用的信号转导途径中的作用。
Ann N Y Acad Sci. 2009 Apr;1160:99-104. doi: 10.1111/j.1749-6632.2009.03828.x.
10
Relaxin family peptide receptors--from orphans to therapeutic targets.松弛素家族肽受体——从孤儿受体到治疗靶点
Drug Discov Today. 2008 Aug;13(15-16):640-51. doi: 10.1016/j.drudis.2008.04.002. Epub 2008 Jun 6.

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