甲状旁腺激素受体的非经典信号转导。
Non-canonical signaling of the PTH receptor.
机构信息
Laboratory for GPCR Biology, Department of Pharmacology and Chemical Biology, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15261, USA.
出版信息
Trends Pharmacol Sci. 2012 Aug;33(8):423-31. doi: 10.1016/j.tips.2012.05.004. Epub 2012 Jun 16.
Abstract
The classical model of arrestin-mediated desensitization of cell-surface G-protein-coupled receptors (GPCRs) is thought to be universal. However, this paradigm is incompatible with recent reports that the parathyroid hormone (PTH) receptor (PTHR), a crucial GPCR for bone and mineral ion metabolism, sustains G(S) activity and continues to generate cAMP for prolonged periods after ligand washout; during these periods the receptor is observed mainly in endosomes, associated with the bound ligand, G(S) and β-arrestins. In this review we discuss possible molecular mechanisms underlying sustained signaling by the PTHR, including modes of signal generation and attenuation within endosomes, as well as the biological relevance of such non-canonical signaling.
摘要
细胞表面 G 蛋白偶联受体 (GPCR) 的经典抑制素介导脱敏模型被认为是普遍存在的。然而，这一范例与最近的研究结果相矛盾，即甲状旁腺激素 (PTH) 受体 (PTHR) 是骨和矿物质离子代谢的关键 GPCR，它在配体洗脱后持续维持 G(S) 活性并继续产生 cAMP 延长时间；在这些时期，受体主要存在于与结合配体、G(S) 和β抑制素相关的内体中。在这篇综述中，我们讨论了 PTHR 持续信号转导的可能分子机制，包括内体中信号产生和衰减的模式，以及这种非典型信号转导的生物学相关性。
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本文引用的文献
1
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Annu Rev Pharmacol Toxicol. 2012;52:179-97. doi: 10.1146/annurev.pharmtox.010909.105800. Epub 2011 Sep 19.
2
Endocytosis promotes rapid dopaminergic signaling.内吞作用促进多巴胺能信号的快速传递。
Neuron. 2011 Jul 28;71(2):278-90. doi: 10.1016/j.neuron.2011.05.036.
3
Emerging paradigms of β-arrestin-dependent seven transmembrane receptor signaling.β-arrestin 依赖性七跨膜受体信号转导的新兴范式。
Trends Biochem Sci. 2011 Sep;36(9):457-69. doi: 10.1016/j.tibs.2011.06.003. Epub 2011 Jul 20.
4
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Trends Pharmacol Sci. 2011 Aug;32(8):443-50. doi: 10.1016/j.tips.2011.04.002. Epub 2011 May 24.
5
Endocytosis and signaling.内吞作用和信号转导。
Curr Opin Cell Biol. 2011 Aug;23(4):393-403. doi: 10.1016/j.ceb.2011.03.008. Epub 2011 Apr 5.
6
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7
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Cell Mol Life Sci. 2011 Jan;68(1):1-13. doi: 10.1007/s00018-010-0465-9. Epub 2010 Aug 12.
8
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9
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Mol Endocrinol. 2009 Dec;23(12):2048-59. doi: 10.1210/me.2008-0436. Epub 2009 Oct 16.
10
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Curr Genomics. 2009 Apr;10(2):133-42. doi: 10.2174/138920209787847014.
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