ArticleThe Journal of biological chemistry2008
Insulin-like growth factor-I stimulates Shc-dependent phosphatidylinositol 3-kinase activation via Grb2-associated p85 in vascular smooth muscle cells.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Pooled it
- Vascular Smooth Muscle Cells: A Therapeutic Target in Atherosclerosis.Reviews in cardiovascular medicine · 2025Review
- The Deficits of Insulin Signal in Alzheimer's Disease and the Mechanisms of Vanadium Compounds in Curing AD.Current issues in molecular biology · 2023Review
- The Strategies for Treating "Alzheimer's Disease": Insulin Signaling May Be a Feasible Target.Current issues in molecular biology · 2022Review
- BCATc modulates crosstalk between the PI3K/Akt and the Ras/ERK pathway regulating proliferation in triple negative breast cancer.Oncotarget · 2020Article
- Hyperglycemia induces vascular smooth muscle cell dedifferentiation by suppressing insulin receptor substrate-1-mediated p53/KLF4 complex stabilization.The Journal of biological chemistry · 2019Article
- Inhibition of Aberrant IGF-I Signaling in Diabetic Male Rat Retina Prevents and Reverses Changes of Diabetic Retinopathy.Journal of diabetes research · 2019Article
- Sonic hedgehog signaling regulates hypoxia/reoxygenation-induced H9C2 myocardial cell apoptosis.Experimental and therapeutic medicine · 2018Article
- HER2 Amplification in Tumors Activates PI3K/Akt Signaling Independent of HER3.Cancer research · 2018Article
- Evolving mechanisms of vascular smooth muscle contraction highlight key targets in vascular disease.Biochemical pharmacology · 2018Review
- LRP1 integrates murine macrophage cholesterol homeostasis and inflammatory responses in atherosclerosis.eLife · 2017Article
- PPARβ/δ, a Novel Regulator for Vascular Smooth Muscle Cells Phenotypic Modulation and Vascular Remodeling after Subarachnoid Hemorrhage in Rats.Scientific reports · 2017Article
- Down-regulation of Insulin Receptor Substrate 1 during Hyperglycemia Induces Vascular Smooth Muscle Cell Dedifferentiation.The Journal of biological chemistry · 2017Article
- Protein Kinase C as Regulator of Vascular Smooth Muscle Function and Potential Target in Vascular Disorders.Advances in pharmacology (San Diego, Calif.) · 2017Review
- IRS-1 Functions as a Molecular Scaffold to Coordinate IGF-I/IGFBP-2 Signaling During Osteoblast Differentiation.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2016Article
- Insulin-like growth factor-I and insulin-like growth factor binding protein-1 are related to cardiovascular disease biomarkers in obese adolescents.Pediatric diabetes · 2016Article
- ShcA Protects against Epithelial-Mesenchymal Transition through Compartmentalized Inhibition of TGF-β-Induced Smad Activation.PLoS biology · 2015Article
- The coordinate cellular response to insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-2 (IGFBP-2) is regulated through vimentin binding to receptor tyrosine phosphatase β (RPTPβ).The Journal of biological chemistry · 2015Article
- Receptor tyrosine kinase (RTK) signalling in the control of neural stem and progenitor cell (NSPC) development.Molecular neurobiology · 2014Review
- Recruitment of Nox4 to a plasma membrane scaffold is required for localized reactive oxygen species generation and sustained Src activation in response to insulin-like growth factor-I.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Insulin-like growth factor-I (IGF-I) stimulates vascular smooth muscle cell proliferation and migration by activating both MAPK and phosphatidylinositol 3-kinase (PI3K). Vascular smooth muscle cells (VSMCs) maintained in 25 mm glucose sustain MAPK activation via increased Shc phosphorylation and Grb2 association resulting in an enhanced mitogenic response compared with cells grown in 5 mm glucose. PI3K plays a major role in IGF-I-stimulated VSMC migration, and hyperglycemia augments this response. In contrast to MAPK activation the role of Shc in modulating PI3K in response to IGF-I has not been determined. In this study we show that impaired Shc association with Grb2 results in decreased Grb2-p85 association, SHPS-1-p85 recruitment, and PI3K activation in response to IGF-I. Exposure of VSMCs to cell-permeable peptides, which contained polyproline sequences from p85 proposed to mediate Grb2 association, resulted in inhibition of Grb2-p85 binding and AKT phosphorylation. Transfected cells that expressed p85 mutant that had specific prolines mutated to alanines resulted in less Grb2-p85 association, and a Grb2 mutant (W36A/W193A) that attenuated p85 binding showed decreased association of p85 with SHPS-1, PI3K activation, AKT phosphorylation, cell proliferation, and migration in response to IGF-I. Cellular exposure to 25 mm glucose, which is required for Shc phosphorylation in response to IGF-I, resulted in enhanced Grb2 binding to p85, activation of PI3K activity, and increased AKT phosphorylation as compared with cells exposed to 5 mm glucose. We conclude that in VSMCs exposed to hyperglycemia, IGF-I stimulation of Shc facilitates the transfer of Grb2 to p85 resulting in enhanced PI3K activation and AKT phosphorylation leading to enhanced cell proliferation and migration.
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What OpenQuestion holds
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.