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dc.contributor.authorGuilherme, Adilson L.
dc.contributor.authorCzech, Michael P.
dc.date2022-08-11T08:10:04.000
dc.date.accessioned2022-08-23T16:54:05Z
dc.date.available2022-08-23T16:54:05Z
dc.date.issued1998-12-05
dc.date.submitted2008-08-04
dc.identifier.citation<p>J Biol Chem. 1998 Dec 11;273(50):33119-22.</p>
dc.identifier.issn0021-9258 (Print)
dc.identifier.doi10.1074/jbc.273.50.33119
dc.identifier.pmid9837876
dc.identifier.urihttp://hdl.handle.net/20.500.14038/42420
dc.description.abstractThe signal transduction pathway by which insulin stimulates glucose transport is not understood, but a role for complexes of insulin receptor substrate (IRS) proteins and phosphatidylinositol (PI) 3-kinase as well as for Akt/protein kinase B (PKB) has been proposed. Here, we present evidence suggesting that formation of IRS-1/PI 3-kinase complexes and Akt/PKB activation are insufficient to stimulate glucose transport in rat adipocytes. Cross-linking of beta1-integrin on the surface of rat adipocytes by anti-beta1-integrin antibody and fibronectin was found to cause greater IRS-1 tyrosine phosphorylation, IRS-1-associated PI 3-kinase activity, and Akt/PKB activation, detected by anti-serine 473 antibody, than did 1 nM insulin. Clustering of beta1-integrin also significantly potentiated stimulation of insulin receptor and IRS-1 tyrosine phosphorylation, IRS-associated PI 3-kinase activity, and Akt/PKB activation caused by submaximal concentrations of insulin. In contrast, beta1-integrin clustering caused neither a change in deoxyglucose transport nor an effect on the ability of insulin to stimulate deoxyglucose uptake at any concentration along the entire dose-response relationship range. The data suggest that (i) beta1-integrins can engage tyrosine kinase signaling pathways in isolated fat cells, potentially regulating fat cell functions and (ii) either formation of IRS-1/PI 3-kinase complexes and Akt/PKB activation is not necessary for regulation of glucose transport in fat cells or an additional signaling pathway is required.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=9837876&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1074/jbc.273.50.33119
dc.subject1-Phosphatidylinositol 3-Kinase
dc.subjectAdipocytes
dc.subjectAnimals
dc.subjectAntigens, CD29
dc.subjectBiological Transport
dc.subjectEnzyme Activation
dc.subjectGlucose
dc.subjectMale
dc.subjectOncogene Protein v-akt
dc.subjectPhosphoproteins
dc.subjectPhosphorylation
dc.subjectRats
dc.subjectRats, Sprague-Dawley
dc.subjectReceptor, Insulin
dc.subjectRetroviridae Proteins, Oncogenic
dc.subject*Signal Transduction
dc.subjectTyrosine
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleStimulation of IRS-1-associated phosphatidylinositol 3-kinase and Akt/protein kinase B but not glucose transport by beta1-integrin signaling in rat adipocytes
dc.typeJournal Article
dc.source.journaltitleThe Journal of biological chemistry
dc.source.volume273
dc.source.issue50
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/771
dc.identifier.contextkey564686
html.description.abstract<p>The signal transduction pathway by which insulin stimulates glucose transport is not understood, but a role for complexes of insulin receptor substrate (IRS) proteins and phosphatidylinositol (PI) 3-kinase as well as for Akt/protein kinase B (PKB) has been proposed. Here, we present evidence suggesting that formation of IRS-1/PI 3-kinase complexes and Akt/PKB activation are insufficient to stimulate glucose transport in rat adipocytes. Cross-linking of beta1-integrin on the surface of rat adipocytes by anti-beta1-integrin antibody and fibronectin was found to cause greater IRS-1 tyrosine phosphorylation, IRS-1-associated PI 3-kinase activity, and Akt/PKB activation, detected by anti-serine 473 antibody, than did 1 nM insulin. Clustering of beta1-integrin also significantly potentiated stimulation of insulin receptor and IRS-1 tyrosine phosphorylation, IRS-associated PI 3-kinase activity, and Akt/PKB activation caused by submaximal concentrations of insulin. In contrast, beta1-integrin clustering caused neither a change in deoxyglucose transport nor an effect on the ability of insulin to stimulate deoxyglucose uptake at any concentration along the entire dose-response relationship range. The data suggest that (i) beta1-integrins can engage tyrosine kinase signaling pathways in isolated fat cells, potentially regulating fat cell functions and (ii) either formation of IRS-1/PI 3-kinase complexes and Akt/PKB activation is not necessary for regulation of glucose transport in fat cells or an additional signaling pathway is required.</p>
dc.identifier.submissionpathoapubs/771
dc.contributor.departmentProgram in Molecular Medicine and Department of Biochemistry and Molecular Biology
dc.source.pages33119-22


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