Abstract |
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.
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Authors | Zhongjian Xie, Jian Peng, Sally D Pennypacker, Ying Chen |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 399
Issue 3
Pg. 425-8
(Aug 27 2010)
ISSN: 1090-2104 [Electronic] United States |
PMID | 20674545
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Copyright 2010 Elsevier Inc. All rights reserved. |
Chemical References |
- Inositol 1,4,5-Trisphosphate Receptors
- Epidermal Growth Factor
- EGFR protein, human
- ErbB Receptors
- Phospholipase C gamma
- Calcium
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Topics |
- Calcium
(metabolism)
- Catalysis
- Cell Line, Tumor
- Cell Movement
- Epidermal Growth Factor
(metabolism, pharmacology)
- ErbB Receptors
(metabolism)
- Humans
- Inositol 1,4,5-Trisphosphate Receptors
(agonists, metabolism)
- Neoplasm Invasiveness
- Phospholipase C gamma
(metabolism)
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