Activation of Vav and Ras through the nerve growth factor and B cell receptors by different kinases

Engagement of the B-cell antigen receptor (BCR) or the nerve growth factor receptor (NGFR/TrkA) induces activation of multiple tyrosine kinases, resul ting in phosphorylation of numerous intracellular substrates. We show that addition of NGF or anti-IgM antibody leads to the early tyrosine phosphoryl ation of p95(vav), which is expressed exclusively in hematopoietic cells; N GF, similar to crosslinking the BCR, also results in the rapid activation o f Ras. The phosphorylation of Vav and activation of Ras triggered by NGF is mediated through Trk tyrosine kinase, whereas signaling through the BCR us es a different tyrosine kinase. We also show that NGF induces tyrosine phos phorylation of Shc and its association with Grb2. Vav and Ras with the adap tor proteins Shc and Grb2 appear to serve as a link between different recep tor-mediated signaling pathways and, in human B cells, may play an importan t regulatory role in neuroimmune interactions. (C) 1999 Academic Press.