The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307)
- PMID: 10722755
- DOI: 10.1074/jbc.275.12.9047
The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307)
Abstract
Tumor necrosis factor alpha (TNFalpha) inhibits insulin action, in part, through serine phosphorylation of IRS proteins; however, the phosphorylation sites that mediate the inhibition are unknown. TNFalpha promotes multipotential signal transduction cascades, including the activation of the Jun NH(2)-terminal kinase (JNK). Endogenous JNK associates with IRS-1 in Chinese hamster ovary cells. Anisomycin, a strong activator of JNK in these cells, stimulates the activity of JNK bound to IRS-1 and inhibits the insulin-stimulated tyrosine phosphorylation of IRS-1. Serine 307 is a major site of JNK phosphorylation in IRS-1. Mutation of serine 307 to alanine eliminates phosphorylation of IRS-1 by JNK and abrogates the inhibitory effect of TNFalpha on insulin-stimulated tyrosine phosphorylation of IRS-1. These results suggest that phosphorylation of serine 307 might mediate, at least partially, the inhibitory effect of proinflammatory cytokines like TNFalpha on IRS-1 function.
Similar articles
-
Tumor necrosis factor alpha-mediated insulin resistance, but not dedifferentiation, is abrogated by MEK1/2 inhibitors in 3T3-L1 adipocytes.Mol Endocrinol. 2000 Oct;14(10):1557-69. doi: 10.1210/mend.14.10.0542. Mol Endocrinol. 2000. PMID: 11043572
-
Salicylic acid reverses phorbol 12-myristate-13-acetate (PMA)- and tumor necrosis factor alpha (TNFalpha)-induced insulin receptor substrate 1 (IRS1) serine 307 phosphorylation and insulin resistance in human embryonic kidney 293 (HEK293) cells.J Biol Chem. 2003 Jan 3;278(1):180-6. doi: 10.1074/jbc.M205565200. Epub 2002 Oct 29. J Biol Chem. 2003. PMID: 12409308
-
Sequential phosphorylation of insulin receptor substrate-2 by glycogen synthase kinase-3 and c-Jun NH2-terminal kinase plays a role in hepatic insulin signaling.Am J Physiol Endocrinol Metab. 2008 Feb;294(2):E307-15. doi: 10.1152/ajpendo.00534.2007. Epub 2007 Nov 20. Am J Physiol Endocrinol Metab. 2008. PMID: 18029441
-
[Elucidation of a New Mechanism of Onset of Insulin Resistance: Effects of Statins and Tumor Necrosis Factor-α on Insulin Signal Transduction].Yakugaku Zasshi. 2018;138(11):1329-1334. doi: 10.1248/yakushi.18-00116. Yakugaku Zasshi. 2018. PMID: 30381640 Review. Japanese.
-
The insulin signaling system.J Biol Chem. 1994 Jan 7;269(1):1-4. J Biol Chem. 1994. PMID: 8276779 Review. No abstract available.
Cited by
-
Propranolol improves impaired hepatic phosphatidylinositol 3-kinase/akt signaling after burn injury.Mol Med. 2012 May 9;18(1):707-11. doi: 10.2119/molmed.2011.00277. Mol Med. 2012. PMID: 22396018 Free PMC article.
-
Role of lipotoxicity in endothelial dysfunction.Heart Fail Clin. 2012 Oct;8(4):589-607. doi: 10.1016/j.hfc.2012.06.012. Epub 2012 Aug 10. Heart Fail Clin. 2012. PMID: 22999242 Free PMC article. Review.
-
Therapeutic Opportunities in Damage-Associated Molecular Pattern-Driven Metabolic Diseases.Antioxid Redox Signal. 2015 Dec 10;23(17):1305-15. doi: 10.1089/ars.2015.6383. Epub 2015 Jul 27. Antioxid Redox Signal. 2015. PMID: 26055926 Free PMC article. Review.
-
Discovery of potent and selective covalent inhibitors of JNK.Chem Biol. 2012 Jan 27;19(1):140-54. doi: 10.1016/j.chembiol.2011.11.010. Chem Biol. 2012. PMID: 22284361 Free PMC article.
-
Evidence for tuning adipocytes ICER levels for obesity care.Adipocyte. 2012 Jul 1;1(3):157-160. doi: 10.4161/adip.20000. Adipocyte. 2012. PMID: 23700525 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Research Materials
Miscellaneous
