Lck regulates Vav activation of members of the Rho family of GTPases

Mol Cell Biol. 1997 Mar;17(3):1346-53. doi: 10.1128/MCB.17.3.1346.

Abstract

Vav is a member of a family of oncogene proteins that share an approximately 250-amino-acid motif called a Dbl homology domain. Paradoxically, Dbl itself and other proteins containing a Dbl domain catalyze GTP-GDP exchange for Rho family proteins, whereas Vav has been reported to catalyze GTP-GDP exchange for Ras proteins. We present Saccharomyces cerevisiae genetic data, in vitro biochemical data, and animal cell biological data indicating that Vav is a guanine nucleotide exchange factor for Rho-related proteins, but in similar genetic and biochemical experiments we fail to find evidence that Vav is a guanine nucleotide exchange factor for Ras. Further, we present data indicating that the Lck kinase activates the guanine nucleotide exchange factor and transforming activity of Vav.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Line
  • Fibroblasts
  • GTP-Binding Proteins / metabolism*
  • Guanine Nucleotide Exchange Factors*
  • Guanosine Diphosphate / metabolism
  • Humans
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Phosphorylation
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-vav
  • Pseudopodia
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / physiology
  • Saccharomyces cerevisiae Proteins*
  • Signal Transduction / physiology*
  • Suppression, Genetic
  • cdc42 GTP-Binding Protein
  • rac GTP-Binding Proteins
  • ras Proteins / metabolism
  • rhoA GTP-Binding Protein
  • src-Family Kinases / metabolism*

Substances

  • CDC24 protein, S cerevisiae
  • Cell Cycle Proteins
  • Guanine Nucleotide Exchange Factors
  • MCF2 protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-vav
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • VAV1 protein, human
  • Vav1 protein, rat
  • Guanosine Diphosphate
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • src-Family Kinases
  • GTP-Binding Proteins
  • cdc42 GTP-Binding Protein
  • rac GTP-Binding Proteins
  • ras Proteins
  • rhoA GTP-Binding Protein