Multiple phosphorylation sites in RGS16 differentially modulate its GAP activity
Multiple phosphorylation sites in RGS16 differentially modulate its GAP activity
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DOI：
10.1016/s0014-5793(01)02757-0
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发表时间：
2001-08-24
期刊：
影响因子：
3.5
通讯作者：
Lin, SC
中科院分区：
文献类型：
--
作者：
Chen, CH;Wang, HS;Lin, SC
G蛋白信号调节蛋白(RGS)是激活Gα亚基的GTP酶激活蛋白(GAP)。我们发现，小鼠Rgs16在HEK293T细胞中表达时，基于体内正磷酸盐标记实验，在丝氨酸194处被结构性磷酸化，而在表达α2A肾上腺素能受体的细胞中，丝氨酸53在肾上腺素刺激下以一种配体依赖的方式被磷酸化。这两个位点上的磷酸化都会削弱其GAP活性，并随后减弱异源三聚体G蛋白刺激的细胞外信号调节蛋白激酶活性。这是第一个通过G蛋白偶联受体磷酸化来下调RGS功能的报道。(C)2001年欧洲生化学会联合会。爱思唯尔科学公司出版。版权所有。
Regulators of G-protein signaling (RGS) are GTPase-activating proteins (GAP) for activated G alpha subunits. We found that mouse RGS16, when expressed in HEK293T cells, is phosphorylated constitutively at serine 194 based on in vivo orthophosphate labeling experiments, while serine 53 is phosphorylated in a ligand-dependent manner upon stimulation by epinephrine in cells expressing the alpha 2A adrenergic receptor. Phosphorylation on both sites impairs its GAP activity and subsequent attenuation on heterotrimeric G-protein-stimulated extracellular signal-regulated protein kinase activity. This is the first report of RGS functional downregulation by phosphorylation via a G-protein-coupled receptor. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.