G Protein-Coupled Receptor Signaling Through β-Arrestin-Dependent Mechanisms.
G Protein-Coupled Receptor Signaling Through β-Arrestin-Dependent Mechanisms.
复制标题
DOI：
10.1097/fjc.0000000000000482
复制
发表时间：
2017-09
影响因子：
3
通讯作者：
Shenoy SK
中科院分区：
文献类型：
--
作者：
Jean-Charles PY;Kaur S;Shenoy SK
β-arrestin 1（或arrestin 2）和β-arrestin 2（或arrestin 3）是广泛表达的胞质衔接蛋白，最初发现它们通过异源三聚体G蛋白在G蛋白偶联受体（GPCR）信号传导中起抑制作用。然而，进一步的生物化学表征显示，β-抑制蛋白不仅“阻断”活化的GPCR，而且触发内吞作用和激酶活化，导致可以定位于内体上的特异性信号传导途径。还发现β-arrestins启动的信号通路不依赖于GPCR对G蛋白的激活。阻断G蛋白活化但促进β-arrestin结合的配体的发现，或反之亦然，提示了选择性激活细胞内信号通路的令人兴奋的可能性。此外，越来越明显的是，β-抑制蛋白依赖性信号传导是极其多样的，即使涉及相同的效应激酶，也会通过不同的GPCR引起不同的细胞应答。本文综述了β-arrestins介导的各种信号通路，并重点介绍了β-arrestins依赖性信号通路的生理效应。
β-arrestin1 (or arrestin2) and β-arrestin2 (or arrestin3) are ubiquitously expressed cytosolic adaptor proteins that were originally discovered for their inhibitory role in G protein-coupled receptor (GPCR) signaling via heterotrimeric G proteins. However, further biochemical characterization revealed that β-arrestins do not just ‘block’ the activated GPCRs, but trigger endocytosis and kinase activation leading to specific signaling pathways that can be localized on endosomes. The signaling pathways initiated by β-arrestins were also found to be independent of G protein activation by GPCRs. The discovery of ligands that blocked G protein activation but promoted β-arrestin binding, or vice-versa, suggested the exciting possibility of selectively activating intracellular signaling pathways. Additionally, it is becoming increasingly evident that β-arrestin-dependent signaling is extremely diverse and provokes distinct cellular responses through different GPCRs even when the same effector kinase is involved. In this review, we summarize various signaling pathways mediated by β-arrestins and highlight the physiologic effects of β-arrestin-dependent signaling.