c-Jun N-terminal kinase (JNK) mediates feedback inhibition of the insulin signaling cascade.
作者： Yong Hee Lee , Jodel Giraud , Roger J. Davis , Morris F. White
关键词: IRS1 、 Tyrosine phosphorylation 、 Internal medicine 、 Insulin 、 c-jun 、 Cell biology 、 Endocrinology 、 Insulin receptor substrate 、 Kinase 、 Phosphorylation 、 Insulin receptor 、 Chemistry
摘要: Activation of the c-Jun N-terminal kinase (JNK) by proinflammatory cytokines inhibits insulin signaling, at least in part, stimulating phosphorylation rat/mouse receptor substrate 1 (Irs1) Ser307(Ser312 human IRS1). Here we show that JNK mediated feedback inhibition signal mouse embryo fibroblasts, 3T3-L1 adipocytes, and 32DIR cells. Insulin stimulation activity required phosphatidylinositol 3-kinase Grb2 signaling. Moreover, activation was inhibited a cell-permeable peptide disrupted interaction with cellular proteins. However, direct binding to Irs1 not for its insulin, whereas Ser307 Irs1. Insulin-stimulated reduced 80% cells lacking JNK1 JNK2 or expressing mutant protein site. Reduced Ser307phosphorylation directly related increased insulin-stimulated tyrosine phosphorylation, Akt glucose uptake. These results support hypothesis is negative regulator action phosphorylating
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