Phosphatidylinositol-3,4,5-trisphosphate (PtdIns-3,4,5-P3)/Tec kinase-dependent calcium signaling pathway: a target for SHIP-mediated inhibitory signals.
|Title||Phosphatidylinositol-3,4,5-trisphosphate (PtdIns-3,4,5-P3)/Tec kinase-dependent calcium signaling pathway: a target for SHIP-mediated inhibitory signals.|
|Publication Type||Journal Article|
|Year of Publication||1998|
|Authors||Scharenberg AM, El-Hillal O, Fruman DA, Beitz LO, Li Z, Lin S, Gout I, Cantley LC, Rawlings DJ, Kinet JP|
|Journal||The EMBO journal|
|Date Published||1998 Apr 1|
|Keywords||Animals, Blood Proteins, Calcium, Cell Line, Transformed, Enzyme Activation, Enzyme Inhibitors, Fibroblasts, Inositol Phosphates, Isoenzymes, Mutation, Phosphatidylinositol 3-Kinases, Phosphatidylinositol Phosphates, Phospholipase C gamma, Phosphoproteins, Phosphoric Monoester Hydrolases, Phosphorylation, Protein-Tyrosine Kinases, Rats, Receptors, Antigen, B-Cell, Receptors, IgG, Sequence Homology, Amino Acid, Signal Transduction, Type C Phospholipases, Tyrosine|
Tec family non-receptor tyrosine kinases have been implicated in signal transduction events initiated by cell surface receptors from a broad range of cell types, including an essential role in B-cell development. A unique feature of several Tec members among known tyrosine kinases is the presence of an N-terminal pleckstrin homology (PH) domain. We directly demonstrate that phosphatidylinositol-3,4,5-trisphosphate (PtdIns-3,4,5-P3) interacting with the PH domain acts as an upstream activation signal for Tec kinases, resulting in Tec kinase-dependent phospholipase Cgamma (PLCgamma) tyrosine phosphorylation and inositol trisphosphate production. In addition, we show that this pathway is blocked when an SH2-containing inositol phosphatase (SHIP)-dependent inhibitory receptor is engaged. Together, our results suggest a general mechanism whereby PtdIns-3,4,5-P3 regulates receptor-dependent calcium signals through the function of Tec kinases.
|Alternate Journal||EMBO J.|