JNK/SAPK activation by platelet-derived growth factor in A431 cells requires both the phospholipase C-gamma and the phosphatidylinositol 3-kinase signaling pathways of the receptor.
Wild-type or mutant betaPDGF receptors were introduced into A431 cells that lack endogenous PDGF receptors. PDGF stimulates JNK1 activity in a dose- and time-dependent manner in cells expressing the wild-type receptor. A receptor mutant lacking all the binding sites for SHP-2, GAP, PI3K, and PLC-gamma fails to activate JNK1. Receptor mutants with no binding site for either SHP-2 or GAP can fully activate JNK1 but those which do not bind either PI3K or PLC-gamma are unable to induce JNK1 activation. PDGF-dependent JNK1 activation was reduced upon cell pretreatment with wortmannin or GF109203X and is completely abrogated by chronic PMA stimulation. Altogether, these results indicate that PDGF activates JNK1 through a pathway that involves both PI3K and PLC-gamma and subsequent activation of protein kinase C.
Assefa
Z
Z
Faculty of Medicine, KU Leuven, Herestraat 49, Leuven, B-3000, Belgium.
Valius
M
M
Vántus
T
T
Agostinis
P
P
Merlevede
W
W
Vandenheede
J R
JR
D000730:Androstadienes / Q000494:pharmacology; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*; D000077191:Wortmannin
D000730:Androstadienes; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004791:Enzyme Inhibitors; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010982:Platelet-Derived Growth Factor; D011493:Protein Kinase C; D017479:Receptors, Platelet-Derived Growth Factor; D013755:Tetradecanoylphorbol Acetate; D010738:Type C Phospholipases; D000077191:Wortmannin