The SH3 domain, but not the catalytic domain, is required for phospholipase C-gamma1 to mediate epidermal growth factor-induced mitogenesis.
Phospholipase C-gamma1 (PLC-gamma1) 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-gamma1 is required for EGF-induced mitogenesis of squamous cell carcinoma (SCC) cells, but the mitogenic function of PLC-gamma1 is independent of its lipase activity. Earlier studies suggest that the Src homology 3 (SH3) domain of PLC-gamma1 possesses mitogenic activity. In the present study, we sought to determine the role of the SH3 domain of PLC-gamma1 in EGF-induced SCC cell mitogenesis. We examined the effect of overexpression of PLC-gamma1, a catalytically active PLC-gamma1 mutant lacking the SH3 domain or a catalytically inactive PLC-gamma1 mutant lacking the X domain on EGF-induced SCC4 (tongue squamous cell carcinoma) cell mitogenesis. We found that overexpression of PLC-gamma1 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-gamma1 to mediate EGF-induced SCC4 cell mitogenesis.
Xie
Zhongjian
Z
Endocrine Unit, Veterans Affairs Medical Center, Northern California Institute for Research and Education, University of California, San Francisco, CA 94121, USA. Zhongjian.Xie@gmail.com
Chen
Ying
Y
Pennypacker
Sally D
SD
Zhou
Zhiguang
Z
Peng
Dan
D
D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000473:pathology*; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008938:Mitosis; D051966:Phospholipase C gamma / Q000235:genetics / Q000378:metabolism*; D018909:src Homology Domains
D004815:Epidermal Growth Factor; D051966:Phospholipase C gamma