β-arrestin signaling and regulation of transcription
β-arrestin signaling and regulation of transcription
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DOI：
10.1242/jcs.03338
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发表时间：
2007-01-15
影响因子：
4
通讯作者：
Pei, Gang
中科院分区：
文献类型：
--
作者：
Ma, Lan;Pei, Gang
β-抑制蛋白1和β-抑制蛋白2是众所周知的G蛋白偶联受体（GPCR）信号传导的负调节剂。在GPCR激活后，β-抑制蛋白易位至细胞膜并结合激动剂占据的受体。这使这些受体与G蛋白解偶联并促进它们的内化，从而引起脱敏。然而，越来越多的证据表明，β-抑制蛋白也作为支架蛋白，与几种细胞质蛋白相互作用，并将GPCR连接到细胞内信号通路，如MAPK级联。最近的工作还揭示，响应于某些GPCR的激活，β-抑制蛋白从细胞质易位到细胞核，并在靶基因的启动子处与转录辅因子如p300和cAMP反应元件结合蛋白（CREB）结合以促进转录。它们还在细胞质中与转录因子如I κ B α和MDM 2的调节因子相互作用并间接调节转录。这种β-抑制蛋白介导的转录调节似乎在细胞生长、凋亡和免疫功能调节中起重要作用。
beta-arrestin 1 and beta-arrestin 2 are well-known negative regulators of G-protein-coupled receptor ( GPCR) signaling. Upon GPCR activation, beta-arrestins translocate to the cell membrane and bind to the agonist-occupied receptors. This uncouples these receptors from G proteins and promotes their internalization, thus causing desensitization. However, accumulating evidence indicates that beta-arrestins also function as scaffold proteins that interact with several cytoplasmic proteins and link GPCRs to intracellular signaling pathways such as MAPK cascades. Recent work has also revealed that, in response to activation of certain GPCRs, beta-arrestins translocate from the cytoplasm to the nucleus and associate with transcription cofactors such as p300 and cAMP-response element-binding protein ( CREB) at the promoters of target genes to promote transcription. They also interact with regulators of transcription factors, such as I kappa B alpha and MDM2, in the cytoplasm and regulate transcription indirectly. This beta-arrestin-mediated regulation of transcription appears to play important roles in cell growth, apoptosis and modulation of immune functions.