title: A novel GTPase-activating protein for Rho interacts with a PDZ domain of the protein-tyrosine phosphatase PTPL1.
abstract: 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.
authors.affiliation: Ludwig Institute for Cancer Research, Box 595, Biomedical Centre, S-751 24 Uppsala, Sweden. Jan.Saras@LICR.uu.se
authors.forename: J
authors.initials: J
authors.lastname: Saras
authors.forename: P
authors.initials: P
authors.lastname: Franzén
authors.forename: P
authors.initials: P
authors.lastname: Aspenström
authors.forename: U
authors.initials: U
authors.lastname: Hellman
authors.forename: L J
authors.initials: LJ
authors.lastname: Gonez
authors.forename: C H
authors.initials: CH
authors.lastname: Heldin
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004789:Enzyme Activation; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D008969:Molecular Sequence Data; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; D020690:GTPase-Activating Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D017027:Protein Tyrosine Phosphatases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins