ArticleMolecular and cellular biology2001
Insulin receptor substrate 3 (IRS-3) and IRS-4 impair IRS-1- and IRS-2-mediated signaling.
Article in Molecular and cellular biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 112 citations in OpenAlex.
- Molecular Characteristics of the Endometrium in Polycystic Ovary Syndrome with Insulin Resistance.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Identification of shared biomarkers in obesity and non-alcoholic fatty liver disease: a comprehensive analysis of Mendelian randomization and transcriptomic data.Frontiers in nutrition · 2026Article
- Novel differentially expressed genes and multiple biological pathways for Alzheimer's disease identified in brain tissue from African American donors.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Preeclampsia as a Study Model for Aging: The Klotho Gene Paradigm.International journal of molecular sciences · 2025Review
- Recent progress in bone-repair strategies in diabetic conditions.Materials today. Bio · 2023Review
- Is MG53 a potential therapeutic target for cancer?Frontiers in endocrinology · 2023Review
- Review
- Chronic venous disease patients show increased IRS-4 expression in the great saphenous vein wall.The Journal of international medical research · 2021Article
- The Placenta as a Target for Alcohol During Pregnancy: The Close Relation with IGFs Signaling Pathway.Reviews of physiology, biochemistry and pharmacology · 2021Review
- Diagnosis and Management of Central Congenital Hypothyroidism.Frontiers in endocrinology · 2021Review
- Local delivery of insulin/IGF-1 for bone regeneration: carriers, strategies, and effects.Nanotheranostics · 2020Review
- Fractionated whole body gamma irradiation modulates the hepatic response in type II diabetes of high fat diet model rats.Molecular biology reports · 2019Article
- Mutations in IRS4 are associated with central hypothyroidism.Journal of medical genetics · 2018Article
- Analysis of human ES cell differentiation establishes that the dominant isoforms of the lncRNAs RMST and FIRRE are circular.BMC genomics · 2018Article
- IRS4, a novel modulator of BMP/Smad and Akt signalling during early muscle differentiation.Scientific reports · 2017Article
- Endotoxemia-mediated activation of acetyltransferase P300 impairs insulin signaling in obesity.Nature communications · 2017Article
- IRS4 induces mammary tumorigenesis and confers resistance to HER2-targeted therapy through constitutive PI3K/AKT-pathway hyperactivation.Nature communications · 2016Article
- The MicroRNA miR-191 Supports T Cell Survival Following Common γ Chain Signaling.The Journal of biological chemistry · 2016Article
- CDK4 is an essential insulin effector in adipocytes.The Journal of clinical investigation · 2016Article
- Defect of insulin signal in peripheral tissues: Important role of ceramide.World journal of diabetes · 2014Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
To investigate the roles of insulin receptor substrate 3 (IRS-3) and IRS-4 in the insulin-like growth factor 1 (IGF-1) signaling cascade, we introduced these proteins into 3T3 embryonic fibroblast cell lines prepared from wild-type (WT) and IRS-1 knockout (KO) mice by using a retroviral system. Following transduction of IRS-3 or IRS-4, the cells showed a significant decrease in IRS-2 mRNA and protein levels without any change in the IRS-1 protein level. In these cell lines, IGF-1 caused the rapid tyrosine phosphorylation of all four IRS proteins. However, IRS-3- or IRS-4-expressing cells also showed a marked decrease in IRS-1 and IRS-2 phosphorylation compared to the host cells. This decrease was accounted for in part by a decrease in the level of IRS-2 protein but occurred with no significant change in the IRS-1 protein level. IRS-3- or IRS-4-overexpressing cells showed an increase in basal phosphatidylinositol 3-kinase activity and basal Akt phosphorylation, while the IGF-1-stimulated levels correlated well with total tyrosine phosphorylation level of all IRS proteins in each cell line. IRS-3 expression in WT cells also caused an increase in IGF-1-induced mitogen-activated protein kinase phosphorylation and egr-1 expression ( approximately 1.8- and approximately 2.4-fold with respect to WT). In the IRS-1 KO cells, the impaired mitogenic response to IGF-1 was reconstituted with IRS-1 to supranormal levels and was returned to almost normal by IRS-2 or IRS-3 but was not improved by overexpression of IRS-4. These data suggest that IRS-3 and IRS-4 may act as negative regulators of the IGF-1 signaling pathway by suppressing the function of other IRS proteins at several steps.
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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.