Endocrine Unit, Veterans Affairs Medical Center, Northern California Institute for Research and Education, University of California, San Francisco, CA 94121, USA.
Biochem Biophys Res Commun. 2010 Aug 27;399(3):425-8. doi: 10.1016/j.bbrc.2010.07.098. Epub 2010 Jul 30.
Phospholipase C-gamma1 (PLC-gamma1), a tyrosine kinase substrate, has been implicated in the pathway for the epidermal growth factor receptor (EGFR)-induced cell migration. However, the underlying mechanism by which PLC-gamma1 mediates EGFR-induced cell migration remains elusive. In the present study, we sought to determine whether the lipase activity of PLC-gamma1 is required for EGFR-induced cell migration. We found that overexpression of PLC-gamma1 in squamous cell carcinoma SCC4 cells markedly enhanced EGF-induced PLC-gamma1 activation, intracellular calcium rise, and cell migration. This enhancement was abolished by mutational inactivation of the catalytic domain of PLC-gamma1. Inhibition of the downstream signaling processes mediated by the activity of phospholipase C (PLC) using IP(3) receptor inhibitor or intracellular calcium chelator blocked EGF-induced cell migration. These data indicate that EGF-induced cell migration is mediated by the lipase domain of PLC-gamma1 and the subsequent IP(3) generation and intracellular calcium mobilization.
PLC-γ1（磷脂酶 C-γ1）是一种酪氨酸激酶底物，它参与了表皮生长因子受体（EGFR）诱导的细胞迁移途径。然而，PLC-γ1介导 EGFR 诱导的细胞迁移的潜在机制仍不清楚。在本研究中，我们试图确定 PLC-γ1 的脂酶活性是否是 EGFR 诱导的细胞迁移所必需的。我们发现，在鳞状细胞癌细胞 SCC4 中过表达 PLC-γ1 可显著增强 EGF 诱导的 PLC-γ1 激活、细胞内钙升高和细胞迁移。这种增强作用被 PLC-γ1 的催化结构域的突变失活所消除。使用 IP3 受体抑制剂或细胞内钙螯合剂抑制由 PLC 活性介导的下游信号转导过程可阻断 EGF 诱导的细胞迁移。这些数据表明，EGF 诱导的细胞迁移是由 PLC-γ1 的脂酶结构域及其随后的 IP3 生成和细胞内钙动员介导的。
