PHOSPHATIDYLINOSITOL-3,4,5-TRISPHOSPHATE (PTDINS-3,4,5-P-3) TEC KINASE-DEPENDENT CALCIUM SIGNALING PATHWAY - A TARGET FOR SHIP-MEDIATED INHIBITORY SIGNALS

Tec family non-receptor tyrosine kinases have been implicated in signa l transduction events initiated by cell surface receptors from a broad range of cell types, including an essential role in B-cell developmen t. A unique feature of several Tec members among known tyrosine kinase s is the presence of an N-terminal pleckstrin homology (PH) domain. We directly demonstrate that phosphatidylinositol-3,3,5-trisphosphate (P tdIns-3,3,5-P-3) interacting with the PH domain acts as an upstream ac tivation signal for Tec kinases, resulting in Tec kinase-dependent pho spholipase Cy (PLC gamma) tyrosine phosphorylation and inositol trisph osphate production. In addition, we show that this pathway is blocked when an SH2-containing inositol phosphatase (SHIP)-dependent inhibitor y receptor is engaged. Together, our results suggest a general mechani sm whereby PtdIns-3,4,5-P-3 regulates receptor-dependent calcium signa ls through the function of Tec kinases.