A non-receptor tyrosine kinase that inhibits the GTPase activity of p21cdc42

Nature. 1993 May 27;363(6427):364-7. doi: 10.1038/363364a0.


The Ras-related Rho subfamily of GTP-binding proteins (p21s), which includes Rho, Rac and Cdc42Hs, is implicated in different aspects of cytoskeletal organization. These proteins behave like Ras (p21ras) in that their active GTP-bound form is inactivated by intrinsic hydrolysis of the nucleotide gamma-phosphate, which can be stimulated by GTPase-activating proteins (GAPs). We have previously shown that there is a diversity of GAPs that recognize this subfamily, including n-chimaerin, which is enriched in the hippocampus; we also detected proteins that bind these p21 proteins and seem to inhibit GTP hydrolysis. We now report the characterization of a hippocampal complementary DNA encoding a tyrosine kinase that specifically binds Cdc42Hs in its GTP-bound form. This binding is mediated by a unique sequence of 47 amino acids C-terminal to an SH3 domain and inhibits both the intrinsic and GAP-stimulated GTPase activity of Cdc42Hs. Our findings indicate that there may be a regulatory mechanism that sustains the GTP-bound active form of Cdc42Hs and which is directly linked to a tyrosine phosphorylation pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Cloning, Molecular
  • GTP Phosphohydrolases / antagonists & inhibitors*
  • GTP-Binding Proteins / antagonists & inhibitors*
  • GTPase-Activating Proteins
  • Hippocampus / metabolism
  • Humans
  • Molecular Sequence Data
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Phosphorylation
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Proteins / antagonists & inhibitors
  • Proteins / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid
  • cdc42 GTP-Binding Protein
  • ras GTPase-Activating Proteins


  • GTPase-Activating Proteins
  • Peptide Fragments
  • Proteins
  • Recombinant Fusion Proteins
  • ras GTPase-Activating Proteins
  • Cdc42Hs-associated kinase
  • Protein-Tyrosine Kinases
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • cdc42 GTP-Binding Protein

Associated data

  • GENBANK/L13738