Epidermal growth factor-induced phosphoinositide hydrolysis. Modulation by protein kinase C.
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)P4. The increased Ins(1,4,5)P3/Ins(1,3,4,5)P4 formation in the PDBu long-term pretreated cells was coincident with the increased Ca2+ 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.
Vicentini
L M
LM
Department of Pharmacology, University of Milano, Italy.
Cervini
R
R
Zippel
R
R
Mantegazza
P
P
D002712:Chlorides / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology; D018021:Lithium Chloride; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D002712:Chlorides; D007295:Inositol Phosphates; D010703:Phorbol Esters; D010716:Phosphatidylinositols; C081655:inositol-1,3,4,5-tetrakisphosphate; D015240:Phorbol 12,13-Dibutyrate; D004815:Epidermal Growth Factor; D015544:Inositol 1,4,5-Trisphosphate; D008094:Lithium; D011493:Protein Kinase C; D018021:Lithium Chloride