ArticleApoptosis : an international journal on programmed cell death2009
Insulin receptor substrate (IRS)-2, not IRS-1, protects human neuroblastoma cells against apoptosis.
Article in Apoptosis : an international journal on programmed cell death, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Active pyruvate dehydrogenase and impaired gluconeogenesis in orthotopic hepatomas of rats.Metabolism: clinical and experimental · 2019Article
- Sequential testicular atrophy involves changes in cellular proliferation and apoptosis associated with variations in aromatase P450 expression levels in Irs-2-deficient mice.Journal of anatomy · 2019Article
- Integrated proximal proteomics reveals IRS2 as a determinant of cell survival in ALK-driven neuroblastoma.Science signaling · 2018Article
- Selective gene dependencies in MYCN-amplified neuroblastoma include the core transcriptional regulatory circuitry.Nature genetics · 2018Article
- IL-4 and IL-13 Receptor Signaling From 4PS to Insulin Receptor Substrate 2: There and Back Again, a Historical View.Frontiers in immunology · 2018Review
- Insulin-like growth factor-1 deficiency and metabolic syndrome.Journal of translational medicine · 2016Review
- Insulin Receptor Substrate Adaptor Proteins Mediate Prognostic Gene Expression Profiles in Breast Cancer.PloS one · 2016Article
- miR-106a* inhibits the proliferation of renal carcinoma cells by targeting IRS-2.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- The Novel Functions of High-Molecular-Mass Complexes Containing Insulin Receptor Substrates in Mediation and Modulation of Insulin-Like Activities: Emerging Concept of Diverse Functions by IRS-Associated Proteins.Frontiers in endocrinology · 2015Review
- Characterization of genetic lesions in rhabdomyosarcoma using a high-density single nucleotide polymorphism array.Cancer science · 2013Article
- Cell survival signaling in neuroblastoma.Anti-cancer agents in medicinal chemistry · 2013Review
- Quantitative phosphoproteomic analysis identifies activation of the RET and IGF-1R/IR signaling pathways in neuroblastoma.PloS one · 2013Article
- Article
- Aldosterone enhances IGF-I-mediated signaling and biological function in vascular smooth muscle cells.Endocrinology · 2010Article
- Insulin-like growth factor-I-stimulated insulin receptor substrate-1 negatively regulates Src homology 2 domain-containing protein-tyrosine phosphatase substrate-1 function in vascular smooth muscle cells.The Journal of biological chemistry · 2010Article
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2 authors.
Funding
Abstract
Insulin receptor substrates (IRS)-1 and -2 are major substrates of insulin and type I insulin-like growth factor (IGF-I) receptor (IGF-IR) signaling. In this study, SH-EP human neuroblastoma cells are used as a model system to examine the differential roles of IRS-1 and IRS-2 on glucose-mediated apoptosis. In the presence of high glucose, IRS-1 underwent caspase-mediated degradation, followed by focal adhesion kinase (FAK) and Akt degradation and apoptosis. IRS-2 expression blocked all these changes whereas IRS-1 overexpression had no effect. In parallel, IRS-2, but not IRS-1, overexpression enhanced IGF-I-mediated Akt activation without affecting extracellular regulated kinase signaling. While IRS-1 was readily degraded by caspases, hyperglycemia-mediated IRS-2 degradation was unaffected by caspase inhibitors but blocked by proteasome and calpain inhibitors. Our data suggest that the differential degradation of IRS-1 and IRS-2 contributes to their distinct modes of action and the increased neuroprotective effects of IRS-2 in this report are due, in part, to its resistance to caspase-mediated degradation.
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