Phosphorylation of Ser307 in Insulin Receptor Substrate-1 Blocks Interactions with the Insulin Receptor and Inhibits Insulin Action
TLDR
In 32D myeloid progenitor cells, phosphorylation of Ser307 inhibited insulin stimulation of the phosphatidylinositol 3-kinase and MAPK cascades, suggesting that inhibition of PTB domain function in IRS-1 by phosphorylated Ser307 might be a general mechanism to regulate insulin signaling.About:
This article is published in Journal of Biological Chemistry.The article was published on 2002-01-11 and is currently open access. It has received 961 citations till now. The article focuses on the topics: Insulin Receptor Substrate Proteins & Insulin receptor substrate.read more
Citations
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Inflammation and insulin resistance
TL;DR: The evolving concept of insulin resistance and T2D as having immunological components and an improving picture of how inflammation modulates metabolism provide new opportunities for using antiinflammatory strategies to correct the metabolic consequences of excess adiposity.
Journal ArticleDOI
Inflammation, stress, and diabetes
TL;DR: The molecular and cellular underpinnings of obesity-induced inflammation and the signaling pathways at the intersection of metabolism and inflammation that contribute to diabetes are discussed.
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Oxidative Stress and Stress-Activated Signaling Pathways: A Unifying Hypothesis of Type 2 Diabetes
TL;DR: A unifying hypothesis is proposed whereby hyperglycemia and FFA-induced activation of the nuclear factor-kappaB, p38 MAPK, and NH2-terminal Jun kinases/stress-activated protein kinases stress pathways plays a key role in causing late complications in type 1 and type 1 diabetes, along with insulin resistance and impaired insulin secretion in type 2 diabetes.
Journal ArticleDOI
From endoplasmic-reticulum stress to the inflammatory response
Kezhong Zhang,Randal J. Kaufman +1 more
TL;DR: New observations suggest that the unfolded-protein response can initiate inflammation, and the coupling of these responses in specialized cells and tissues is now thought to be fundamental in the pathogenesis of inflammatory diseases.
Journal ArticleDOI
Obesity, inflammation, and insulin resistance.
TL;DR: The rapidly expanding body of animal and clinical data that support potential roles for inflammation in the pathogenesis of insulin resistance and type 2 diabetes mellitus are reviewed.
References
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JNK1: A protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain
Benoit Dérijard,Benoit Dérijard,Masahiko Hibi,I-Huan Wu,I-Huan Wu,Tamera Barrett,Bing Su,Tiliang Deng,Michael Karin,Roger J. Davis,Roger J. Davis +10 more
TL;DR: JNK1 is a component of a novel signal transduction pathway that is activated by oncoproteins and UV irradiation and its properties indicate that JNK1 activation may play an important role in tumor promotion.
Journal ArticleDOI
Obesity and insulin resistance
Barbara B. Kahn,Jeffrey S. Flier +1 more
TL;DR: Recent progress in understanding of the adipo-insulin axis is reviewed, areas of controversy or uncertainty are highlighted, and approaches to clarifying the unresolved issues are suggested.
Journal ArticleDOI
Cellular mechanisms of insulin resistance
TL;DR: It is shown that commonly accepted models that attempt to explain the association of insulin resistance and obesity are incompatible with recent findings and an alternative model is proposed that appears to fit these and other available data.
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IRS-1-Mediated Inhibition of Insulin Receptor Tyrosine Kinase Activity in TNF-α- and Obesity-Induced Insulin Resistance
Gökhan S. Hotamisligil,Pascal Peraldi,Adriane I. Budavari,Ramsey Ellis,Morris F. White,Bruce M. Spiegelman +5 more
TL;DR: Results indicate that TNF-α induces insulin resistance through an unexpected action of IRS-1 to attenuate insulin receptor signaling.
Journal ArticleDOI
Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein.
Xiao Jian Sun,P. Rothenberg,P. Rothenberg,C R Kahn,Jonathan M. Backer,E. Araki,P. A. Wilden,D. A. Cahill,Barry J. Goldstein,Morris F. White +9 more
TL;DR: During insulin stimulation, the IRS-1 protein undergoes tyrosine phosphorylation and binds phosphatidylinositol 3-kinase, suggesting that IRS–1 acts as a multisite Mocking' protein to bind signal-transducing molecules containing Src-homology 2 and SRC-Homology-3 domains, which may link the insulin receptor kinase and enzymes regulating cellular growth and metabolism.