| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1931617 | Biochemical and Biophysical Research Communications | 2010 | 4 Pages |
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.
Research highlights► Overexpression of phospholipase C-γ1 (PLC-γ1) enhances epidermal growth factor (EGF)-induced intracellular calcium rise and cell migration. ► The enhancement of EGF-induced intracellular calcium rise and cell migration is abolished by inactivation of the catalytic activity of PLC-γ1. ► Inhibition of the IP3 receptor activity and chelation of intracellular calcium block EGF-induced migration.
