Abstract
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.
MeSH terms
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Androstadienes / pharmacology
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Animals
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Blotting, Western
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CHO Cells
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Cricetinae
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Enzyme Activation / drug effects
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Enzyme Inhibitors / pharmacology
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Gene Expression*
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Humans
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Insulin / pharmacology*
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JNK Mitogen-Activated Protein Kinases
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Kinetics
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases*
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Phosphatidylinositol 3-Kinases / physiology
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Phosphoinositide-3 Kinase Inhibitors
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Receptor, Insulin / genetics*
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Receptor, Insulin / physiology
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Wortmannin
Substances
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Androstadienes
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Enzyme Inhibitors
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Insulin
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Phosphoinositide-3 Kinase Inhibitors
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Receptor, Insulin
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Calcium-Calmodulin-Dependent Protein Kinases
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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Wortmannin