The mechanism involved in the regulation of phospholipase Cγ1 activity in cell migration
The mechanism involved in the regulation of phospholipase Cγ1 activity in cell migration
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DOI：
10.1038/sj.onc.1205821
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发表时间：
2002-09-19
期刊：
影响因子：
8
通讯作者：
Falasca, M
中科院分区：
文献类型：
--
作者：
Piccolo, E;Innominato, PF;Falasca, M
磷脂酶C（PLC）的激活导致第二信使肌醇1，4，5-三磷酸和甘油二酯的形成。酪氨酸激酶受体通过PLC γ同工酶激活该反应。PLC γ活性涉及其与受体酪氨酸激酶的活化和磷酸化。最近，已经表明磷酸肌醇3-激酶（PI 3-K）可以通过PI 3-K产物磷脂酰肌醇3，4，5-三磷酸（PtdIns-3，4，5-P-3）和PLC γ普列克底物蛋白同源（PH）结构域的相互作用来调节PLC γ活性。在努力了解信号通路，涉及PI 3-K调节PLC γ，我们发现，表皮生长因子诱导PI 3-K依赖性易位PLC γ 1在前沿的迁移细胞在伤口愈合试验。类似地，分离的PH，但不是PLC γ 1的Src同源（SH）结构域，N-SH 2或SH 3，在前缘易位。我们的实验还表明，稳定的PH PLC γ 1表达阻断表皮生长因子（EGF）和血清诱导的细胞运动，并增加细胞粘附在MDA-MB-231细胞。这可能表明PI 3-K对PLC γ 1的影响可能与细胞迁移有关，其中PLC γ 1似乎通过调节一系列涉及肌动蛋白聚合的事件而发挥关键作用。
Activation of the enzyme phospholipase C (PLC) leads to the formation of second messengers inositol 1,4,5-trisphosphate and diacylglycerol. Tyrosine kinase receptors activate this reaction through PLCgamma isoenzymes. PLCgamma activity involves its activation with, and phosphorylation by, receptor tyrosine kinases. Recently, it has been shown that phosphoinositide 3-kinase (PI 3-K) may regulate PLCgamma activity through the interaction of the PI 3-K product phosphatidylinositol 3,4,5-trisphosphate (PtdIns-3,4,5-P-3) and the PLCgamma pleckstrin homology (PH) domain. In an effort to understand the signalling pathway that involves PI 3-K regulation of PLCgamma, we found that EGF induces a PI 3-K-dependent translocation of PLCgamma1 at the leading edge of migrating cells in a wound healing assay. Similarly, the isolated PH, but not the Src-homology (SH) domains, N-SH2 or SH3, of PLCgamma1, translocates at the leading edge. Our experiments also showed that stable PH PLCgamma1 expression blocks epidermal growth factor (EGF)- and serum-induced cell motility and increases cell adhesion in MDA-MB-231 cells. This may suggest that influence of PI 3-K on PLCgamma1 could be relevant in cell migration, where PLCgamma1 seems to play a key role by modulating a series of events involved in actin polymerization.