Regulation of G protein-mediated signal transduction by RGS proteins.
Regulation of G protein-mediated signal transduction by RGS proteins.
复制标题
RGS 蛋白调节 G 蛋白介导的信号转导。
DOI：
10.1016/s0024-3205(01)01020-7
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发表时间：
2001
期刊：
影响因子：
6.1
通讯作者：
T. Kozasa
中科院分区：
文献类型：
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作者：
T. Kozasa
RGS蛋白是一个新的G蛋白信号调节蛋白家族。它们含有约120个氨基酸的同源核心结构域（RGS结构域）。RGS结构域与活化的Gα亚基相互作用。几种RGS蛋白已被生物化学证明作为其相互作用的Gα亚基的GT3激活蛋白（GAP）。除了RGS结构域之外，RGS蛋白在大小、氨基酸序列和组织分布上显著不同。此外，许多RGS蛋白具有参与细胞信号传导的其他蛋白质-蛋白质相互作用基序。我们已经证明，p115 RhoGEF，一个新发现的鸟嘌呤核苷酸交换因子（GEF）的RhoGTdR，有一个RGS结构域在其N-末端区域，该结构域作为一个特定的GAP为Gα12和Gα13。此外，激活的Gα13与该RGS结构域的结合刺激p115 RhoGEF的GEF活性。活化的Gα12抑制Gα13刺激的GEF活性。因此，p115 RhoGEF是异源三聚体G蛋白和RhoGT 3之间的直接连接，除了作为Gα12和Gα13的GAP外，它还作为Gα12和Gα13的效应物发挥作用。我们还发现G蛋白受体激酶2（GRK 2）N端的RGS结构域与Gαq/11特异性相互作用，抑制Gα q介导的PLC-β的活化，这显然是通过隔离活化的Gαq实现的。然而，与其他RGS蛋白不同，该RGS结构域对Gαq不显示显著的GAP活性。这些结果表明，RGS蛋白具有比简单地充当GAP更多样化的功能，并且每个RGS蛋白的功能的表征对于理解细胞中的G蛋白信号网络至关重要。
RGS proteins form a new family of regulatory proteins of G protein signaling. They contain homologous core domains (RGS domains) of about 120 amino acids. RGS domains interact with activated Gα subunits. Several RGS proteins have been shown biochemically to act as GTPase activating proteins (GAPs) for their interacting Gα subunits. Other than RGS domains, RGS proteins differ significantly in size, amino acid sequences, and tissue distribution. In addition, many RGS proteins have other protein-protein interaction motifs involved in cell signaling. We have shown that p115RhoGEF, a newly identified GEF(guanine nucleotide exchange factor) for RhoGTPase, has a RGS domain at its N-terminal region and this domain acts as a specific GAP for Gα12 and Gα13. Furthermore, binding of activated Gα13 to this RGS domain stimulated GEF activity of p115RhoGEF. Activated Gα12 inhibited Gα13-stimulated GEF activity. Thus p115RhoGEF is a direct link between heterotrimeric G protein and RhoGTPase and it functions as an effector for Gα12 and Gα13 in addition to acting as their GAP. We also found that RGS domain at N-terminal regions of G protein receptor kinase 2 (GRK2) specifically interacts with Gαq/11 and inhibits Gαq-mediated activation of PLC-β, apparently through sequestration of activated Gαq. However, unlike other RGS proteins, this RGS domain did not show significant GAP activity to Gαq. These results indicate that RGS proteins have far more diverse functions than acting simply as GAPs and the characterization of function of each RGS protein is crucial to understand the G protein signaling network in cells.