Critical role for the catalytic activity of phospholipase C-gamma1 in epidermal growth factor-induced cell migration.
Critical role for the catalytic activity of phospholipase C-gamma1 in epidermal growth factor-induced cell migration.
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DOI：
10.1016/j.bbrc.2010.07.098
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发表时间：
2010-08-27
影响因子：
3.1
通讯作者：
Chen, Ying
中科院分区：
文献类型：
--
作者：
Xie, Zhongjian;Peng, Jian;Pennypacker, Sally D.;Chen, Ying
磷脂酶C-γ1（PLC-γ1）是一种酪氨酸激酶底物，参与表皮生长因子受体（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的脂肪酶活性是否是EGFR诱导的细胞迁移所必需的。我们发现PLC-γ1在鳞状细胞癌SCC-4细胞中的过表达显著增强EGF诱导的PLC-γ1活化、细胞内钙升高和细胞迁移。PLC-γ1催化结构域的突变失活消除了这种增强作用。用IP 3受体抑制剂或胞内钙离子螯合剂抑制磷脂酶C（PLC）活性介导的下游信号传导过程，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的脂肪酶结构域介导的，随后产生IP 3和细胞内钙动员。
Phospholipase C-γ1 (PLC-γ1), 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-γ1 mediates EGFR-induced cell migration remains elusive. In the present study, we sought to determine whether the lipase activity of PLC-γ1 is required for EGFR-induced cell migration. We found that overexpression of PLC-γ1 in squamous cell carcinoma SCC4 cells markedly enhanced EGF-induced PLC-γ1 activation, intracellular calcium rise and cell migration. This enhancement was abolished by mutational inactivation of the catalytic domain of PLC-γ1. Inhibition of the downstream signaling processes mediated by the activity of phospholipase C (PLC) using IP3 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-γ1 and the subsequent IP3 generation and intracellular calcium mobilization.
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DOI：
10.1158/1078-0432.ccr-07-4857
发表时间：
2008-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Nozawa H;Howell G;Suzuki S;Zhang Q;Qi Y;Klein-Seetharaman J;Wells A;Grandis JR;Thomas SM
通讯作者：
Thomas SM
影响因子：
7.8
作者：
Mouneimne, Ghassan;Soon, Lilian;DesMarais, Vera;Sidani, Mazen;Song, Xiaoyan;Yip, Shu-Chin;Ghosh, Mousumi;Eddy, Robert;Backer, Jonathan M;Condeelis, John
通讯作者：
Condeelis, John
影响因子：
4.8
作者：
Dittmar, T;Husemann, A;Brandt, BH
通讯作者：
Brandt, BH
影响因子：
7.8
作者：
Sun, HQ;Lin, KM;Yin, HL
通讯作者：
Yin, HL
DOI：
10.1083/jcb.127.3.847
发表时间：
1994-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chen P;Xie H;Sekar MC;Gupta K;Wells A
通讯作者：
Wells A