ArticleJournal of cellular physiology2007
Insulin receptor substrate (IRS)-1 regulates murine embryonic stem (mES) cells self-renewal.
Article in Journal of cellular physiology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 31 citations in OpenAlex.
- Type 2 inflammation drives an airway basal stem cell program through insulin receptor substrate signaling.The Journal of allergy and clinical immunology · 2023Article
- Insulin receptor-mediated signaling regulates pluripotency markers and lineage differentiation.Molecular metabolism · 2018Article
- Article
- IGF1 regulates RUNX1 expression via IRS1/2: Implications for antler chondrocyte differentiation.Cell cycle (Georgetown, Tex.) · 2017Article
- PPAR-γ Agonists As Antineoplastic Agents in Cancers with Dysregulated IGF Axis.Frontiers in endocrinology · 2017Review
- MicroRNAs in breast cancer: oncogene and tumor suppressors with clinical potential.Journal of Zhejiang University. Science. B · 2015Review
- The emerging role of insulin and insulin-like growth factor signaling in cancer stem cells.Frontiers in endocrinology · 2014Review
- An efficient weighted graph strategy to identify differentiation associated genes in embryonic stem cells.PloS one · 2013Article
- Regulation of embryonic stem cell self-renewal and pluripotency by leukaemia inhibitory factor.The Biochemical journal · 2011Review
- Low concentrations of nitric oxide delay the differentiation of embryonic stem cells and promote their survival.Cell death & disease · 2010Article
- microRNA, cell cycle, and human breast cancer.The American journal of pathology · 2010Review
- Pediatric primary central nervous system germ cell tumors of different prognosis groups show characteristic miRNome traits and chromosome copy number variations.BMC genomics · 2010Article
- Expression and function of the insulin receptor substrate proteins in cancer.Cell communication and signaling : CCS · 2009Article
- Dicer-1-dependent Dacapo suppression acts downstream of Insulin receptor in regulating cell division of Drosophila germline stem cells.Development (Cambridge, England) · 2009Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Mouse embryonic stem (mES) cells are pluripotent cells that can be propagated in vitro with leukemia inhibitory factor (LIF) and serum. Intracellular signaling by LIF is principally mediated by activation of STAT-3, although additional pathways for self-renewal have been described. Here, we identified a novel role for Insulin receptor substrate-1 (IRS-1) as a critical factor in mES cells self-renewal and differentiation. IRS-1 is expressed and tyrosyl phosphorylated during mES cells self-renewal. Differentiation of mES cells, by LIF withdrawal, is associated with a marked reduction in IRS-1 expression. Targeting of IRS-1 by si-IRS-1 results in a severe reduction of Oct-4 protein expression and alkaline phosphatase activity, markers of undifferentiated mES cells. IRS-1 targeting does not interfere with LIF-induced STAT-3 phosphorylation, but negatively affects protein kinase B (PKB/AKT) and glycogen synthase kinase-3 (GSK-3beta) phosphorylation, which are downstream effectors of the LIF-mediated PI3K signaling cascade. Targeting of IRS-1 also results in a marked down regulation of Id-1 and Id-2 proteins expression, which are important components for self-renewal of ES cells. Conversely, over expression of IRS-1 inhibits mES cell differentiation. Taken together, these results suggest that expression and activity of IRS-1 are critical to the maintenance of the self-renewal program in mES 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.