Saras J, Franzén P, Aspenström P, Hellman U, Gonez L J, Heldin C H
Ludwig Institute for Cancer Research, Box 595, Biomedical Centre, S-751 24 Uppsala, Sweden.
J Biol Chem. 1997 Sep 26;272(39):24333-8. doi: 10.1074/jbc.272.39.24333.
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, Rac, 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.
PTPL1是一种含有五个PDZ结构域的细胞内蛋白酪氨酸磷酸酶。在此，我们展示了一种新型150 kDa蛋白的克隆，该蛋白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锌离子和二酰基甘油结合结构域，以及一段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、Rac和Cdc42具有活性，但明显更倾向于Rho；我们将该分子称为PTPL1相关的RhoGAP 1，即PARG1。Rho被GAPs失活，并且蛋白酪氨酸磷酸化与Rho信号传导有关。因此，PTPL1和PARG1之间的复合物可能作为Rho信号传导的强大负调节因子，作用于Rho本身以及Rho信号转导途径中的酪氨酸磷酸化成分。
