Forskolin-pretreatment ofA431 cells reduced both intrinsic and epidermal growth factor (EGF)-induced EGF receptor phosphorylation, however, phosphorylation of pospholipase c-γ (PLC-γ) was stimulated under the same conditions. No significant difference was detected in the amount of phosphotyrosine of PLC-γ between two cultures with or without forskolin treatment followed by EGF. On the other hand, phosphorylation of a 47 kDa protein (P47) which cross-reacted with an anti-PLC-y monoclonal antibody, was stimulated by both forskolin and EGF. Phosphorylation was exclusively on serine residues in this case. These results indicate that both PLC-γ and P47 are posphorylated by a cAMP-dependent protein kinase and the EGF-stimulated serine kinase, and suggest that serine phosphorylation of PLC-γ has no effect on ligand-dependent coupling with the EGF receptor.
