Phosphatidylinositol-3,4,5-trisphosphate (PtdIns-3,4,5-P3) Tec kinase-dependent calcium signaling pathway:: a target for SHIP-mediated inhibitory signals
Phosphatidylinositol-3,4,5-trisphosphate (PtdIns-3,4,5-P3) Tec kinase-dependent calcium signaling pathway:: a target for SHIP-mediated inhibitory signals
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DOI：
10.1093/emboj/17.7.1961
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发表时间：
1998-04-01
期刊：
影响因子：
11.4
通讯作者：
Kinet, JP
中科院分区：
文献类型：
--
作者：
Scharenberg, AM;El-Hillal, O;Kinet, JP
TEC家族非受体酪氨酸激酶已与来自广泛细胞类型的细胞表面受体引发的信号转导事件有关，包括在B细胞发育中的重要作用。在已知的酪氨酸激酶中，几个TEC成员的一个独特特征是存在N端Pleckstrin同源（pH）结构域。我们直接证明，与pH结构蛋白相互作用的磷脂酰肌醇-3,3,5-三磷酸（PTDINS-3,3,5-P-3）充当TEC激酶的上游激活信号，导致TEC激酶依赖性磷脂酶Cy（ PLCγ）酪氨酸磷酸化和肌醇三磷酸盐的产生。此外，我们表明，当参与含有SH2的肌醇磷酸酶（船体）依赖性抑制受体时，该途径被阻止。总之，我们的结果提出了一种通用机制，即PTDINS-3,4,5-P-3通过TEC激酶的功能调节受体依赖性钙信号。
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-3,3,5-trisphosphate (PtdIns-3,3,5-P-3) interacting with the PH domain acts as an upstream activation signal for Tec kinases, resulting in Tec kinase-dependent phospholipase Cy (PLC gamma) 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.