Abstract
The epidermal growth factor (EGF) receptor has an important role in cellular proliferation, and the enzymatic activity of phospholipase C (PLC)-gamma1 is regarded to be critical for EGF-induced mitogenesis. In this study, we report for the first time a phospholipase complex composed of PLC-gamma1 and phospholipase D2 (PLD2). PLC-gamma1 is co-immunoprecipitated with PLD2 in COS-7 cells. The results of in vitro binding analysis and co-immunoprecipitation analysis in COS-7 cells show that the Src homology (SH) 3 domain of PLC-gamma1 binds to the proline-rich motif within the Phox homology (PX) domain of PLD2. The interaction between PLC-gamma1 and PLD2 is EGF stimulation-dependent and potentiates EGF-induced inositol 1,4,5-trisphosphate (IP(3)) formation and Ca(2+) increase. Mutating Pro-145 and Pro-148 within the PX domain of PLD2 to leucines disrupts the interaction between PLC-gamma1 and PLD2 and fails to potentiate EGF-induced IP(3) formation and Ca(2+) increase. However, neither PLD2 wild type nor PLD2 mutant affects the EGF-induced tyrosine phosphorylation of PLC-gamma1. These findings suggest that, upon EGF stimulation, PLC-gamma1 directly interacts with PLD2 and this interaction is important for PLC-gamma1 activity.
Highlights
The epidermal growth factor (EGF)1 signaling pathways have been implicated in cellular proliferation and cytoskeletal reorganization [1]
We report for the first time upon the phospholipase complex of phospholipase C (PLC)-␥1 and phospholipase D2 (PLD2)
The communication between PLC-␥1 and PLD has been questioned because EGF stimulation activates PLC-␥1 and PLD2 both and because in each signaling pathway there are common molecules such as protein kinase C (PKC) and PIP2 [22, 23]
Summary
The epidermal growth factor (EGF)1 signaling pathways have been implicated in cellular proliferation and cytoskeletal reorganization [1]. These findings suggest that, upon EGF stimulation, PLC-␥1 directly interacts with PLD2 and this interaction is important for PLC-␥1 activity. EGF stimulation increases PLD activity [25, 26], but the roles of the domains of PLD in EGF signaling have not been identified.
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