Cited by 854Metabolism, Diabetes, and CancerAdipokines, Inflammation, and Metabolic DiseasesPI3K/AKT/mTOR signaling in cancer

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Protein–protein interaction in insulin signaling and the molecular mechanisms of insulin resistance

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Virkamäki, Antti, Ueki, Kohjiro, Kahn, C. Ronald·1999·Journal of Clinical Investigation

DOI 10.1172/jci6609PMC PMC408269

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Abstract

Perspective Figure 1 Schematic illustration of major signaling pathways of insulin action.The phosphorylated insulin receptor binds and phosphorylates IRS proteins and Shc, which bind differentially to various downstream signaling proteins.PI3-kinase is critical for metabolic actions of insulin, such as glucose transport, glycogen synthesis, and protein synthesis, whereas Grb-2/SOS complex, which activates the MAP kinase cascade, is critical in mitogenic response.PI3-kinase probably modulates the mitogenic response as well.This series continues from the March 1999, no.6, issue.

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Background
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“1 Insulin resistance Insulin exerts its biological actions by interacting with a membrane-spanning tyrosine kinase receptor, leading to the recruitment of substrate molecules commonly referred to as docking proteins, including the insulin receptor substrate (IRS) proteins, which signal to both metabolic and mitogenic…”
Background

Authors: Virkamäki, A., Ueki, K., & Kahn, C. R.
Affiliations: Joslin Diabetes Center (US)
Corresponding author: Kahn, C. Ronald
ORCID: Ueki, Kohjiro
Kahn, C. Ronald
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1999-04-01
Volume: 103
Issue: 7
Pages: 931-943
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci6609
PMC: PMC408269
OpenAlex: W2095252238
Cited by: 854
References: 176
Citations by year: 2026: 4 · 2025: 4 · 2024: 15 · 2023: 8 · 2022: 15 · 2021: 12 · 2020: 13 · 2019: 16 · 2018: 13 · 2017: 21 · 2016: 22 · 2015: 26 · 2014: 24 · 2013: 27 · 2012: 31
FWCI: 4.88
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: European Foundation for the Study of Diabetes
National Institutes of Health (DK31036)
National Institute of Diabetes and Digestive and Kidney Diseases (R37DK031036, DK 33201, R01DK031036, DK45935, DK31036, R01DK045935, R01DK033201)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Keywords: insulin signaling, insulin resistance, protein-protein interaction, insulin receptor, Shc, PI3-kinase, MAP kinase cascade, glucose transport, glycogen synthesis, mitogen response
MeSH terms: Animals, Humans, Insulin, Insulin Resistance, Phosphorylation, Protein Binding, Receptor, Insulin, Signal Transduction, Gene Targeting, src Homology Domains, Phosphatidylinositol 3-Kinases

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Protein–protein interaction in insulin signaling and the molecular mechanisms of insulin resistance

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