Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 398, Issue 4, Pages 719-722Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2010.07.007
Keywords
Epidermal growth factor receptor; Phospholipase C-gamma 1; Squamous cell carcinoma; Mitogenesis; SH3 domain; Catalytic domain
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Funding
- National Institutes of Health [1R03DE018001, 1R21DE019529-01A2]
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Phospholipase C-gamma 1 (PLC-gamma 1) is a multiple-domain protein and plays an important role in epidermal growth factor (EGF)-induced cell mitogenesis, but the underlying mechanism is unclear. We have previously demonstrated that PLC-gamma 1 is required for EGF-induced mitogenesis of squamous cell carcinoma (SCC) cells, but the mitogenic function of PLC-gamma 1 is independent of its lipase activity. Earlier studies suggest that the Src homology 3 (SH3) domain of PLC-gamma 1 possesses mitogenic activity. In the present study, we sought to determine the role of the SH3 domain of PLC-gamma 1 in EGF-induced SCC cell mitogenesis. We examined the effect of overexpression of PLC-gamma 1, a catalytically active PLC-gamma 1 mutant lacking the SH3 domain or a catalytically inactive PLC-gamma 1 mutant lacking the X domain on EGF-induced SCC4 (tongue squamous cell carcinoma) cell mitogenesis. We found that overexpression of PLC-gamma 1 enhanced EGF-induced SCC4 cell mitogenesis. This enhancement was abolished by deletion of the SH3 domain but not by deletion of the X catalytic domain. These data suggest that the SH3 domain, but not the catalytic domain, is required for PLC-gamma 1 to mediate EGF-induced SCC4 cell mitogenesis. (c) 2010 Elsevier Inc. All rights reserved.
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