Functional and physical interactions of Syk family kinases with the Vav proto-oncogene product.

Syk family kinases are essential for lymphocyte development and activation. Therefore the identification of their direct effectors is of critical importance. Here, we report that Syk interacts in the yeast two-hybrid system with Vav, a proto-oncogene product exclusively expressed in hematopoietic cells. This interaction was direct, required the catalytic activity ...
of Syk, the SH2 domain of Vav, and tyrosine residues in the linker domain of Syk. Vav also associated with Syk and Zap in antigen receptor-stimulated B or T cells, respectively. Functionally, Vav was phosphorylated by Syk family kinases both in vivo and in vitro. Furthermore, Syk and Vav cooperated to activate NF-AT synergistically. These results indicate that the interaction between Syk family kinases and Vav plays an important role in coupling immune recognition receptors to signaling pathways involved in lymphokine production.
Mesh Terms:
B-Lymphocytes, Binding Sites, Cell Cycle Proteins, DNA-Binding Proteins, Enzyme Precursors, Humans, Intracellular Signaling Peptides and Proteins, Lymphocyte Activation, Lymphocytes, Models, Immunological, NFATC Transcription Factors, Nuclear Proteins, Phosphorylation, Protein Binding, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-vav, Receptors, Antigen, B-Cell, Receptors, Antigen, T-Cell, Recombinant Fusion Proteins, Signal Transduction, T-Lymphocytes, Transcription Factors, ZAP-70 Protein-Tyrosine Kinase, src Homology Domains
Immunity
Date: Dec. 01, 1996
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