Vav3 modulates B cell receptor responses by regulating phosphoinositide 3-kinase activation

J Exp Med. 2002 Jan 21;195(2):189-200. doi: 10.1084/jem.20011571.


To elucidate the mechanism(s) by which Vav3, a new member of the Vav family proteins, participates in B cell antigen receptor (BCR) signaling, we have generated a B cell line deficient in Vav3. Here we report that Vav3 influences phosphoinositide 3-kinase (PI3K) function through Rac1 in that phosphatidylinositol-3,4,5-trisphosphate (PIP3) generation was attenuated by loss of Vav3 or by expression of a dominant negative form of Rac1. The functional interaction between PI3K and Rac1 was also demonstrated by increased PI3K activity in the presence of GTP-bound Rac1. In addition, we show that defects of calcium mobilization and c-Jun NH2-terminal kinase (JNK) activation in Vav3-deficient cells are relieved by deletion of a PIP3 hydrolyzing enzyme, SH2 domain-containing inositol polyphosphate 5'-phosphatase (SHIP). Hence, our results suggest a role for Vav3 in regulating the B cell responses by promoting the sustained production of PIP3 and thereby calcium flux.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / immunology
  • Cell Cycle Proteins*
  • Cell Line
  • Chickens
  • Guanine Nucleotide Exchange Factors
  • Humans
  • Phosphatidylinositol 3-Kinases / immunology*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / immunology*
  • Proto-Oncogene Proteins c-vav
  • Receptors, Antigen, B-Cell / genetics
  • Receptors, Antigen, B-Cell / immunology*
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • rac1 GTP-Binding Protein / genetics
  • rac1 GTP-Binding Protein / immunology


  • Cell Cycle Proteins
  • Guanine Nucleotide Exchange Factors
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-vav
  • Receptors, Antigen, B-Cell
  • VAV3 protein, human
  • Phosphatidylinositol 3-Kinases
  • rac1 GTP-Binding Protein
  • Calcium