TYROSINE KINASE-STIMULATED GUANINE-NUCLEOTIDE EXCHANGE ACTIVITY OF VAV IN T-CELL ACTIVATION

The hematopoietically expressed product of the vav proto-oncogene, Vav , shares homology with guanine nucleotide releasing factors (GRFs) [al so called guanosine diphosphate-dissociation stimulators (GDSs)] that activate Ras-related small guanosine triphosphate (GTP)-binding protei ns. Human T cell lysates or Vav immunoprecipitates possessed GRF activ ity that increased after T cell antigen receptor (TCR)-CD3 triggering; an in vitro-translated Vav fragment that contained the putative GRF d omain was also active. Vav-associated GRF stimulation after TCR-CD3 li gation paralleled its tyrosine phosphorylation; both were blocked by a protein tyrosine kinase (PTK) inhibitor. Vav also was a substrate for the p56lck PTK. Thus, Vav is a PTK-regulated GRF that may be importan t in TCR-CD3-initiated signal transduction through the activation of R as.