Vav1 regulates phospholipase C gamma activation and calcium responses in mast cells

The hematopoietic cell-specific protein Vav1 is a substrate of tyrosine kin ases activated following engagement of many receptors, including Fc epsilon RI. Vav1-deficient mice contain normal numbers of mast cells but respond m ore weakly than their normal counterparts to a passive systemic anaphylaxis challenge. Vav1-deficient bone marrow-derived mast cells also exhibited re duced degranulation and cytokine production, although tyrosine phosphorylat ion of FceRI, Syk, and LAT (linker for activation of T cells) was normal. I n contrast, tyrosine phosphorylation of phospholipase C gamma1 (PLC gamma1) and PLC gamma2 and calcium mobilization were markedly inhibited. Reconstit ution of deficient mast cells with Vav1 restored normal tyrosine phosphoryl ation of PLC gamma1 and PLC gamma2 and calcium responses, Thus, Vav1 is ess ential to Fc epsilon RI-mediated activation of PLC gamma and calcium mobili zation in mast cells, In addition to its known role as an activator of Rac1 GTPases, these findings demonstrate a novel function for Vav1 as a regulat or of PLC gamma -activated calcium signals.