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, resulting in phosphorylation of numerous intracellular substrates. We show that addition of NGF or anti-IgM antibody leads to the early tyrosine phosphorylation of p95(vav), which is expressed exclusively in hematopoietic cells; NGF, similar to crosslinking the BCR, also results in the rapid activation of Ras. The phosphorylation of Vav and activation of Ras triggered by NGF is mediated through Trk tyrosine kinase, whereas signaling through the BCR uses a different tyrosine kinase. We also show that NGF induces tyrosine phosphorylation of Shc and its association with Grb2. Vav and Ras with the adaptor proteins Shc and Grb2 appear to serve as a link between different receptor-mediated signaling pathways and, in human B cells, may play an important regulatory role in neuroimmune interactions.
Melamed
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Department of Pediatrics, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, Colorado, 80206, USA.
Patel
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Brodie
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Gelfand
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D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D001402:B-Lymphocytes / Q000378:metabolism; D018797:Cell Cycle Proteins; D004789:Enzyme Activation; D051380:GRB2 Adaptor Protein; D006801:Humans; D007152:Immunologic Capping; D009414:Nerve Growth Factors / Q000378:metabolism*; D014066:Palatine Tonsil / Q000166:cytology; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051567:Proto-Oncogene Proteins c-vav; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D020917:Receptor, trkA; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014443:Tyrosine / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism*