Examination of the role of serine phosphorylation in phospholipase C-gamma and its related P47 in cAMP-mediated depression of epidermal growth factor signal transduction.

Forskolin-pretreatment of A431 cells reduced both intrinsic and epidermal growth factor (EGF)-induced EGF receptor phosphorylation, however, phosphorylation of phospholipase C-gamma (PLC-gamma) was stimulated under the same conditions. No significant difference was detected in the amount of phosphotyrosine of PLC-gamma 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-gamma monoclonal antibody, was stimulated by both forskolin and EGF. Phosphorylation was exclusively on serine residues in this case. These results indicate that both PLC-gamma and P47 are phosphorylated by a cAMP-dependent protein kinase and the EGF-stimulated serine kinase, and suggest that serine phosphorylation of PLC-gamma has no effect on ligand-dependent coupling with the EGF receptor.