A novel GTPase-activating protein for Rho interacts with a PDZ domain of the protein-tyrosine phosphatase PTPL1
A novel GTPase-activating protein for Rho interacts with a PDZ domain of the protein-tyrosine phosphatase PTPL1
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DOI：
10.1074/jbc.272.39.24333
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发表时间：
1997-09-26
影响因子：
4.8
通讯作者：
Heldin, CH
中科院分区：
文献类型：
--
作者：
Saras, J;Franzen, P;Heldin, CH
PTPL1 是一种细胞内蛋白酪氨酸磷酸酶，包含五个 PDZ 结构域。在这里，我们克隆了一种新型 150 kDa 蛋白质，其 C 末端的四个氨基酸残基与 PTPL1 的第四个 PDZ 结构域特异性相互作用。该分子包含一个 GTP 酶激活蛋白 (GAP) 结构域、一个富含半胱氨酸的假定 Zn2+- 和二酰基甘油结合结构域，以及一个与秀丽隐杆线虫基因 ZK669.1a 产物具有序列同源性的区域。 GAP 结构域在体外对 Rho、Pac 和 Cdc42 有活性，但明显偏爱 Rho；我们将该分子称为 PTPL1 相关 RhoGAP 1、PARG1，Rho 被 GAP 灭活，并且蛋白质酪氨酸磷酸化与 Rho 信号传导有关。因此，PTPL1 和 PARG1 之间的复合物可能充当 Rho 信号传导的强大负调节因子，既作用于 Rho 本身，又作用于 Rho 信号转导途径中的酪氨酸磷酸化成分。
PTPL1 is an intracellular protein-tyrosine phosphatase that contains five PDZ domains. Here, we present the cloning of a novel 150-kDa protein, the four most C-terminal amino acid residues of which specifically interact with the fourth PDZ domain of PTPL1. The molecule contains a GTPase-activating protein (GAP) domain, a cysteine-rich, putative Zn2+- and diacylglycerol-binding domain, and a region of sequence homology to the product of the Caenorhabditis elegans gene ZK669.1a. The GAP domain is active on Rho, Pac, and Cdc42 in vitro but with a clear preference for Rho; we refer to the molecule as PTPL1-associated RhoGAP 1, PARG1, Rho is inactivated by GAPs, and protein-tyrosine phosphorylation has been implicated in Rho signaling. Therefore, a complex between PTPL1 and PARG1 may function as a powerful negative regulator of Rho signaling, acting both on Rho itself and on tyrosine phosphorylated components in the Rho signal transduction pathway.