Journal article
Evidence That IRS-2 Phosphorylation Is Required for Insulin Action in Hepatocytes
The Journal of biological chemistry, Vol.273(28), pp.17491-17497
07/1998
DOI: 10.1074/jbc.273.28.17491
PMID: 9651339
Abstract
Insulin receptor substrates (IRSs) are tyrosine-phosphorylated following stimulation with insulin, insulin-like growth factors (IGFs), and interleukins. A key question is whether different IRSs play different roles to mediate insulin's metabolic and growth-promoting effects. In a novel system of insulin receptor-deficient hepatocytes, insulin fails to (i) stimulate glucose phosphorylation, (ii) enhance glycogen synthesis, (iii) suppress glucose production, and (iv) promote mitogenesis. However, insulin's ability to induce IRS-1 and gab-1 phosphorylation and binding to phosphatidylinositol (PI) 3-kinase is unaffected, by virtue of the compensatory actions of IGF-1 receptors. In contrast, phosphorylation of IRS- 2 and generation of IRS-2/PI 3-kinase complexes are markedly reduced. Thus, absence of insulin receptors selectively reduces IRS-2, but not IRS-1 phosphorylation, and the impairment of IRS-2 activation is associated with lack of insulin effects. To address whether phosphorylation of additional IRSs is also affected, we analyzed phosphotyrosine-containing proteins in PI 3-kinase immunoprecipitates from insulin-treated cells. However, these experiments indicate that IRS-1 and IRS-2 are the main PI 3-kinase-bound proteins in hepatocytes. These data identify IRS-2 as the main effector of both the metabolic and growth-promoting actions of insulin through PI 3- kinase in hepatocytes, and IRS-1 as the main substrate mediating the mitogenic actions of IGF-1 receptors.
Details
- Title: Subtitle
- Evidence That IRS-2 Phosphorylation Is Required for Insulin Action in Hepatocytes
- Creators
- Kristina I. Rother - Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentYumi Imai - University of North Carolina at Chapel HillMatilde Caruso - University of Naples Federico IIFrancesco Beguinot - University of Naples Federico IIPietro Formisano - University of Naples Federico IIDomenico Accili - Eunice Kennedy Shriver National Institute of Child Health and Human Development
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.273(28), pp.17491-17497
- DOI
- 10.1074/jbc.273.28.17491
- PMID
- 9651339
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Language
- English
- Date published
- 07/1998
- Academic Unit
- Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984359907902771
Metrics
17 Record Views