Examination of the role of serine phosphorylation in phospholipase C‐γ and its related P47 in cAMP‐mediated depression of epidermal growth factor receptor signal transduction

Abstract

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.