FUNCTIONAL AND PHYSICAL INTERACTIONS OF SYK FAMILY KINASES WITH THE VAV PROTOONCOGENE PRODUCT

Syk family kinases are essential for lymphocyte development and activa tion. Therefore the identification of their direct effecters is of cri tical 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 cat alytic activity of Syk, the SH2 domain of Vav, and tyrosine residues i n the linker domain of Syk. Vav also associated with Syk and Zap in an tigen receptor-stimulated B or T cells, respectively. Functionally, Va v 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 kinase s and Vav plays an important role in coupling immune recognition recep tors to signaling pathways involved in lymphokine production.