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dc.contributor.authorCherniack, Andrew D.
dc.contributor.authorKlarlund, Jes K.
dc.contributor.authorConway, Bruce R.
dc.contributor.authorCzech, Michael P.
dc.date2022-08-11T08:10:04.000
dc.date.accessioned2022-08-23T16:54:17Z
dc.date.available2022-08-23T16:54:17Z
dc.date.issued1995-01-27
dc.date.submitted2008-08-15
dc.identifier.citation<p>J Biol Chem. 1995 Jan 27;270(4):1485-8.</p>
dc.identifier.issn0021-9258 (Print)
dc.identifier.doi10.1074/jbc.270.4.1485
dc.identifier.pmid7829473
dc.identifier.urihttp://hdl.handle.net/20.500.14038/42467
dc.description.abstractInsulin receptor signaling acutely stimulates GTP loading of p21ras, apparently by mobilizing complexes of Grb2 and the guanine nucleotide exchangers Son-of-sevenless (Sos) 1 and 2 to associate with tyrosine-phosphorylated proteins in the plasma membrane. Here we show that in 32P-labeled 3T3-L1 adipocytes the elevated cellular concentrations of [32P]GTP-bound p21ras in response to insulin return to near basal levels after 20-30 min of hormone stimulation, while insulin receptors remain activated. Lysates of such desensitized cells were quantitatively immunoprecipitated with an antiserum recognizing both Sos1 and Sos2 proteins or a specific anti-Sos2 antiserum. Immunoblot analysis of these precipitates revealed that insulin causes a marked hyperphosphorylation of Sos1 and a 50% decrease in Grb2 associated with Sos proteins under these conditions. Similarly, anti-Grb2 immunoprecipitates of such lysates revealed the presence of decreased Sos1 protein due to insulin action. The disassembly of Grb2 from Sos proteins slightly precedes the time course of p21ras deactivation in response to insulin. These data are consistent with the hypothesis that the dissociation of Grb2 from Sos proteins caused by insulin in 3T3-L1 cells mediates p21ras deactivation and desensitization.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=7829473&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1074/jbc.270.4.1485
dc.subject3T3 Cells
dc.subject*Adaptor Proteins, Signal Transducing
dc.subjectAdipocytes
dc.subjectAnimals
dc.subjectAntibodies
dc.subjectElectrophoresis, Polyacrylamide Gel
dc.subjectGRB2 Adaptor Protein
dc.subjectGuanosine Triphosphate
dc.subjectImmunoblotting
dc.subjectKinetics
dc.subjectMembrane Proteins
dc.subjectMice
dc.subjectPhosphorus Radioisotopes
dc.subjectPhosphorylation
dc.subjectProtein Binding
dc.subjectProteins
dc.subjectProto-Oncogene Proteins p21(ras)
dc.subjectReceptor, Epidermal Growth Factor
dc.subjectReceptor, Insulin
dc.subjectSignal Transduction
dc.subjectSon of Sevenless Proteins
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleDisassembly of Son-of-sevenless proteins from Grb2 during p21ras desensitization by insulin
dc.typeArticle
dc.source.journaltitleThe Journal of biological chemistry
dc.source.volume270
dc.source.issue4
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/813
dc.identifier.contextkey579698
html.description.abstract<p>Insulin receptor signaling acutely stimulates GTP loading of p21ras, apparently by mobilizing complexes of Grb2 and the guanine nucleotide exchangers Son-of-sevenless (Sos) 1 and 2 to associate with tyrosine-phosphorylated proteins in the plasma membrane. Here we show that in 32P-labeled 3T3-L1 adipocytes the elevated cellular concentrations of [32P]GTP-bound p21ras in response to insulin return to near basal levels after 20-30 min of hormone stimulation, while insulin receptors remain activated. Lysates of such desensitized cells were quantitatively immunoprecipitated with an antiserum recognizing both Sos1 and Sos2 proteins or a specific anti-Sos2 antiserum. Immunoblot analysis of these precipitates revealed that insulin causes a marked hyperphosphorylation of Sos1 and a 50% decrease in Grb2 associated with Sos proteins under these conditions. Similarly, anti-Grb2 immunoprecipitates of such lysates revealed the presence of decreased Sos1 protein due to insulin action. The disassembly of Grb2 from Sos proteins slightly precedes the time course of p21ras deactivation in response to insulin. These data are consistent with the hypothesis that the dissociation of Grb2 from Sos proteins caused by insulin in 3T3-L1 cells mediates p21ras deactivation and desensitization.</p>
dc.identifier.submissionpathoapubs/813
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages1485-8


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