ArticleThe Journal of biological chemistry2014
Insulin and metabolic stress stimulate multisite serine/threonine phosphorylation of insulin receptor substrate 1 and inhibit tyrosine phosphorylation.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 103 citations in OpenAlex.
- Peripheral inflammatory biomarkers define biotypes of bipolar depression.Molecular psychiatry · 2021Trial
- The Complex Relation of Branched-Chain Amino Acids and Inflammation in the Obesity and Diabetes Context.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026Review
- High-Fat Diet and a High Amyloid Load Interact to Induce PKC-α Dependent Synaptic Insulin Resistance.Molecular & cellular proteomics : MCP · 2026Article
- Structural and mechanistic basis of mTORC2 activation of protein kinase AKT/PKB.The Biochemical journal · 2026Review
- Development of Insulin and Leptin Resistance in the Mouse Brainstem with Age.Molecular neurobiology · 2026Article
- Impact of Combination Therapy With Caffeine and Naringin on Insulin Resistance and Renal Function in a Nonalcoholic Fatty Liver Disease Rat Model.BioMed research international · 2026Article
- The insulin signalling network.Nature metabolism · 2025Review
- Crossing the Blood-Brain Barrier: Innovations in Receptor- and Transporter-Mediated Transcytosis Strategies.Pharmaceutics · 2025Review
- Article
- Comparative proteomics and micro-RNA analysis of skeletal muscle cell small extracellular vesicles - Unique profiles in cells from severely obese individuals with type 2 diabetesFrontiers in physiology · 2025Article
- Mitochondrial bioenergetics dysfunction in T2DM: linking oxidative stress to insulin resistance.Frontiers in endocrinology · 2025Review
- Phosphorylation Codes in IRS-1 and IRS-2 Are Associated with the Activation/Inhibition of Insulin Canonical Signaling Pathways.Current issues in molecular biology · 2024Review
- Liraglutide Improves Diabetic Cardiomyopathy by Downregulation of Cardiac Inflammatory and Apoptosis Markers.Current drug research reviews · 2024Review
- Assessment of the Immune Response in Patients with Insulin Resistance, Obesity, and Diabetes to COVID-19 Vaccination.Vaccines · 2023Review
- Mechanisms of Oxidative Stress in Metabolic Syndrome.International journal of molecular sciences · 2023Review
- Molecular pathways and nutrigenomic review of insulin resistance development in gestational diabetes mellitus.Frontiers in nutrition · 2023Review
- Sexual dimorphism in the molecular mechanisms of insulin resistance during a critical developmental window in Wistar rats.Cell communication and signaling : CCS · 2022Article
- Structural insights into the pSer/pThr dependent regulation of the SHP2 tyrosine phosphatase in insulin and CD28 signaling.Nature communications · 2022Article
- The Role of Insulin Receptor Substrate Proteins in Bronchopulmonary Dysplasia and Asthma: New Potential Perspectives.International journal of molecular sciences · 2022Review
- The Interplay between Insulin Resistance, Inflammation, Oxidative Stress, Base Excision Repair and Metabolic Syndrome in Nonalcoholic Fatty Liver Disease.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
IRS1 and IRS2 are key substrates of the insulin receptor tyrosine kinase. Mass spectrometry reveals more than 50 phosphorylated IRS1 serine and threonine residues (Ser(P)/Thr(P) residues) in IRS1 from insulin-stimulated cells or human tissues. We investigated a subset of IRS1 Ser(P)/Thr(P) residues using a newly developed panel of 25 phospho-specific monoclonal antibodies (αpS/TmAb(Irs1)). CHO cells overexpressing the human insulin receptor and rat IRS1 were stimulated with insulin in the absence or presence of inhibitors of the PI3K → Akt → mechanistic target of rapamycin (mTOR) → S6 kinase or MEK pathways. Nearly all IRS1 Ser(P)/Thr(P) residues were stimulated by insulin and significantly suppressed by PI3K inhibition; fewer were suppressed by Akt or mTOR inhibition, and none were suppressed by MEK inhibition. Insulin-stimulated Irs1 tyrosine phosphorylation (Tyr(P)(Irs1)) was enhanced by inhibition of the PI3K → Akt → mTOR pathway and correlated with decreased Ser(P)-302(Irs1), Ser(P)-307(Irs1), Ser(P)-318(Irs1), Ser(P)-325(Irs1), and Ser(P)-346(Irs1). Metabolic stress modeled by anisomycin, thapsigargin, or tunicamycin increased many of the same Ser(P)/Thr(P) residues as insulin, some of which (Ser(P)-302(Irs1), Ser(P)-307(Irs1), and four others) correlated significantly with impaired insulin-stimulated Tyr(P)(Irs1). Thus, IRS1 Ser(P)/Thr(P) is an integrated response to insulin stimulation and metabolic stress, which associates with reduced Tyr(P)(Irs1) in CHO(IR)/IRS1 cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.