Epidermal growth factor-induced phosphoinositide hydrolysis Modulation by protein kinase C

Abstract A short-term treatment with phorbol 12,13-dibutyrate (PDBu) was found to inhibit totally the epidermal growth factor (EGF)-stimulated phosphoinositide hydrolysis in A431 cells, whereas long-term pretreatment with PDBu, which is known to down regulate protein kinase C, induced a greater accumulation of the EGF-triggered inositol phosphate accumulation, particularly of Ins(1,3,4,5)P 4 . The increased Ins(1,4,5)P 3 /Ins(1,3,4,5)P 4 formation in the PDBu long-term pretreated cells was coincident with the increased Ca 2+ influx stimulated by EGF in the same cells. Since long-term pretreatment with PDBu was found to enhance the EGF signals, an explanation for the synergism between EGF and phorbol esters in the induction of DNA synthesis is provided.