Cyclic AMP can partially restore platelet-derived growth factor-stimulated prostaglandin E2 biosynthesis, and calcium mobilization in EJ-ras-transformed NIH-3T3 cells.
NIH-3T3 cells transformed by the EJ-ras oncogene display reduced platelet-derived growth factor (PDGF)-stimulated phospholipase C activity as measured by inositol 1,4,5-triphosphate (IP3) synthesis and Ca2+ mobilization. The lack of PDGF-stimulated Ca2+ mobilization in EJ-ras transformed cells is not due to a loss of IP3 sensitivity, because microinjected IP3 elevates intracellular Ca2+. Treatment of EJ-ras transformed cells with cholera toxin or 8-bromo-cyclic AMP, but not pertussis toxin or the beta-subunit of cholera toxin, results in a slight recovery of PDGF-stimulated IP3 synthesis, a marked increase in intracellular Ca2+ mobilization, and an almost complete recovery of prostaglandin E2 biosynthesis. These data suggest that EJ p21-mediated inhibition of PDGF-stimulated intracellular events can be partially and transiently reversed by cyclic AMP.
Olinger
P L
PL
Department of Cell Biology, Upjohn Company, Kalamazoo, Michigan 49001.
Benjamin
C W
CW
Gorman
R R
RR
Connor
J A
JA
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002461:Cell Line, Transformed; D002851:Chromatography, High Pressure Liquid; D000242:Cyclic AMP / Q000502:physiology*; D015232:Dinoprostone / Q000096:biosynthesis*; D007091:Image Processing, Computer-Assisted; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000096:biosynthesis / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000378:metabolism
D001095:Arachidonic Acids; D007295:Inositol Phosphates; D010982:Platelet-Derived Growth Factor; D016718:Arachidonic Acid; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D010738:Type C Phospholipases; D015232:Dinoprostone; D002118:Calcium