Premium
Phosphatidylinositol‐3,4,5‐trisphosphate (PtdIns‐3,4,5‐P 3 )/Tec kinase‐dependent calcium signaling pathway: a target for SHIP‐mediated inhibitory signals
Author(s) -
Scharenberg Andrew M.,
ElHillal Ousama,
Fruman David A.,
Beitz Laurie O.,
Li Zuomei,
Lin Siqi,
Gout Ivan,
Cantley Lewis C.,
Rawlings David J.,
Kinet JeanPierre
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.7.1961
Subject(s) - pleckstrin homology domain , biology , microbiology and biotechnology , signal transduction , kinase , phosphatidylinositol , phosphorylation , tec , inositol , c2 domain , tyrosine phosphorylation , receptor tyrosine kinase , biochemistry , receptor , ionosphere , physics , astronomy , membrane
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‐P 3 ) 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‐P 3 regulates receptor‐dependent calcium signals through the function of Tec kinases.