Critical role for the catalytic activity of phospholipase C-gamma1 in epidermal growth factor-induced cell migration.
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.
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
Peng
Jian
J
Pennypacker
Sally D
SD
Chen
Ying
Y
D002118:Calcium / Q000378:metabolism; D002384:Catalysis; D045744:Cell Line, Tumor; D002465:Cell Movement; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000819:agonists / Q000378:metabolism; D009361:Neoplasm Invasiveness; D051966:Phospholipase C gamma / Q000378:metabolism*
D053496:Inositol 1,4,5-Trisphosphate Receptors; D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors; D051966:Phospholipase C gamma; D002118:Calcium