CD19 AS A MEMBRANE-ANCHORED ADAPTER PROTEIN OF B-LYMPHOCYTES - COSTIMULATION OF LIPID AND PROTEIN-KINASES BY RECRUITMENT OF VAV

CD19 is a coreceptor that amplifies signaling by membrane immunoglobul in (mlg) to promote responses of the B lymphocyte to T-dependent antig ens. Vav is a guanine nucleotide exchange factor for the Rho, Rac, Cdc 42 family of small GTPases. We found that coligating mig and CD19 caus es a synergistic increase in the tyrosine phosphorylation of CD19. Pho sphorylated tyrosine-391 of CD19 binds Vav to mediate a sustained incr ease in intracellular Ca2(+) concentration. This response correlates w ith activation by the CD19-Vav complex of phosphatidylinositol 4-phosp hate 5-kinase for the synthesis of phosphatidylinositol 4,5-bisphospha te. Interaction of CD19 with Vav also mediates the synergistic activat ion of the mitogen-activated protein kinase JNK. Therefore, CD19 is a membrane adaptor protein that recruits Vav for the activation of lipid and protein kinases.