Insulin differentially regulates SAPKs/JNKs and ERKs in CHO cells overexpressing human insulin receptors.
In the present study, we compared the ability of insulin to regulate SAPKs/JNKs and ERKs in CHO cells overexpressing human insulin receptors. We show that acute insulin treatment induced a time-dependent increase both in SAPK/JNK and ERK activity but with distinct kinetics. PI-3-kinase inhibition by wortmannin completely blocked insulin activation of SAPKs/JNKs, whereas it partially decreased ERK activation. Prolonged exposure to insulin caused a marked inhibition of SAPK/JNK activity while it induced a sustained activation of ERKs. Insulin inhibition of SAPKs/JNKs was partly due to decreased tyrosine phosphorylation of JNK2. These data indicate that insulin differentially regulates SAPKs/JNKs and ERKs. Moreover, they provide the first evidence that insulin exerts opposite effects on SAPK/JNK activity according to the time of cell treatment.
Desbois-Mouthon
C
C
INSERM U.402, Faculté de Médecine Saint-Antoine, Paris, France.
Blivet-Van Eggelpoel
M J
MJ
Auclair
M
M
Cherqui
G
G
Capeau
J
J
Caron
M
M
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D006224:Cricetinae; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases; D007700:Kinetics; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011972:Receptor, Insulin / Q000235:genetics* / Q000502:physiology; D000077191:Wortmannin
D000730:Androstadienes; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004791:Enzyme Inhibitors; D007328:Insulin; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011972:Receptor, Insulin; D000077191:Wortmannin