A novel GTPase-activating protein for Rho interacts with a PDZ domain of the protein-tyrosine phosphatase PTPL1

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.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cell Line
  • Cloning, Molecular
  • DNA, Complementary
  • Enzyme Activation
  • GTP Phosphohydrolases / metabolism*
  • GTP-Binding Proteins / metabolism*
  • GTPase-Activating Proteins
  • Molecular Sequence Data
  • Protein Binding
  • Protein Tyrosine Phosphatases / chemistry
  • Protein Tyrosine Phosphatases / metabolism*
  • Proteins / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism


  • DNA, Complementary
  • GTPase-Activating Proteins
  • Proteins
  • Recombinant Fusion Proteins
  • Protein Tyrosine Phosphatases
  • GTP Phosphohydrolases
  • GTP-Binding Proteins

Associated data

  • GENBANK/U90920