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- Title
Phosphatidylinositol-3,4,5-trisphosphate (PtdIns-3,4,5-P<sub>3</sub>)/Tec kinase-dependent calcium signaling pathway: a target for SHIP-mediated inhibitory signals.
- Authors
Scharenberg, Andrew M.; El-Hillal, Ousama; Fruman, David A.; Beitz, Laurie O.; Zuomei Li; Siqi Lin; Gout, Ivan; Cantley, Lewis C.; Rawlings, David J.; Kinet, Jean-Pierre
- Abstract
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 Cγ (PLCγ) 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.
- Publication
EMBO Journal, 1998, Vol 17, Issue 7, p1961
- ISSN
0261-4189
- Publication type
Academic Journal
- DOI
10.1093/emboj/17.7.1961