Chen C, Wang H, Fong C W, Lin S C
Regulatory Biology Group, Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117609, Singapore.
FEBS Lett. 2001 Aug 24;504(1-2):16-22. doi: 10.1016/s0014-5793(01)02757-0.
Regulators of G-protein signaling (RGS) are GTPase-activating proteins (GAP) for activated Galpha 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 alpha2A 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.
G蛋白信号调节因子（RGS）是活化Gα亚基的GTP酶激活蛋白（GAP）。我们发现，基于体内正磷酸盐标记实验，小鼠RGS16在HEK293T细胞中表达时，丝氨酸194会持续磷酸化，而在表达α2A肾上腺素能受体的细胞中，经肾上腺素刺激后，丝氨酸53会以配体依赖的方式磷酸化。两个位点的磷酸化都会损害其GAP活性以及随后对异源三聚体G蛋白刺激的细胞外信号调节蛋白激酶活性的减弱作用。这是关于通过G蛋白偶联受体磷酸化对RGS功能进行下调的首次报道。
