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dc.contributor.authorBaltensperger, Kurt
dc.contributor.authorKaroor, Vijaya
dc.contributor.authorPaul, Hyacinth
dc.contributor.authorRuoho, Arnold E.
dc.contributor.authorCzech, Michael P.
dc.contributor.authorMalbon, Craig C.
dc.date2022-08-11T08:10:04.000
dc.date.accessioned2022-08-23T16:54:14Z
dc.date.available2022-08-23T16:54:14Z
dc.date.issued1996-01-12
dc.date.submitted2008-08-15
dc.identifier.citation<p>J Biol Chem. 1996 Jan 12;271(2):1061-4.</p>
dc.identifier.issn0021-9258 (Print)
dc.identifier.doi10.1074/jbc.271.2.1061
dc.identifier.pmid8557631
dc.identifier.urihttp://hdl.handle.net/20.500.14038/42456
dc.description.abstractG-protein-linked receptors and intrinsic tyrosine-kinase growth receptors represent two prominent modalities in cell signaling. Cross-regulation among members of both receptor superfamilies has been reported, including the counter-regulatory effects of insulin on beta-adrenergic catecholamine action. Cells stimulated by insulin show loss of function and increased phosphotyrosine content of beta 2-adrenergic receptors. Phosphorylation of tyrosyl residues 350/354 of beta 2-adrenergic receptors is obligatory for counter-regulation by insulin (Karoor, V., Baltensperger, K., Paul, H., Czech, M., and Malbon, C. C. (1995) J. Biol. Chem. 270, 25305-25308), suggesting the hypothesis that G-protein-linked receptors themselves may act as substrates for the insulin receptor and other growth factor receptors. This hypothesis was evaluated directly using recombinant human insulin receptor, hamster beta 2-adrenergic receptor, and an vitro reconstitution and phosphorylation assay. Insulin is shown to stimulate insulin receptor-catalyzed phosphorylation of the beta 2-adrenergic receptor. Phosphoamino acid analysis establishes that insulin receptor-catalyzed phosphorylation of the beta 2-adrenergic receptor in vitro is confined to phosphotyrosine. High pressure liquid chromatography and two-dimensional mapping reveal insulin receptor-catalyzed phosphorylation of the beta 2-adrenergic receptor at residues Tyr132/Tyr141, Tyr350/Tyr354, and Tyr364, known sites of phosphorylation in response to insulin in vivo. Insulin-like growth factor-I receptor as well as the insulin receptor displays the capacity to phosphorylate the beta 2-adrenergic receptor in vitro, establishing a new paradigm, i.e. G-protein-linked receptors acting as substrates for intrinsic tyrosine kinase growth factor receptors.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=8557631&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1074/jbc.271.2.1061
dc.subjectAmino Acid Sequence
dc.subjectAnimals
dc.subjectCHO Cells
dc.subjectCricetinae
dc.subjectGTP-Binding Proteins
dc.subjectHumans
dc.subjectMolecular Sequence Data
dc.subjectPhosphorylation
dc.subjectReceptor Protein-Tyrosine Kinases
dc.subjectReceptor, IGF Type 1
dc.subjectReceptor, Insulin
dc.subjectReceptors, Adrenergic, beta-2
dc.subjectRecombinant Proteins
dc.subjectSubstrate Specificity
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleThe beta-adrenergic receptor is a substrate for the insulin receptor tyrosine kinase
dc.typeArticle
dc.source.journaltitleThe Journal of biological chemistry
dc.source.volume271
dc.source.issue2
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/803
dc.identifier.contextkey579688
html.description.abstract<p>G-protein-linked receptors and intrinsic tyrosine-kinase growth receptors represent two prominent modalities in cell signaling. Cross-regulation among members of both receptor superfamilies has been reported, including the counter-regulatory effects of insulin on beta-adrenergic catecholamine action. Cells stimulated by insulin show loss of function and increased phosphotyrosine content of beta 2-adrenergic receptors. Phosphorylation of tyrosyl residues 350/354 of beta 2-adrenergic receptors is obligatory for counter-regulation by insulin (Karoor, V., Baltensperger, K., Paul, H., Czech, M., and Malbon, C. C. (1995) J. Biol. Chem. 270, 25305-25308), suggesting the hypothesis that G-protein-linked receptors themselves may act as substrates for the insulin receptor and other growth factor receptors. This hypothesis was evaluated directly using recombinant human insulin receptor, hamster beta 2-adrenergic receptor, and an vitro reconstitution and phosphorylation assay. Insulin is shown to stimulate insulin receptor-catalyzed phosphorylation of the beta 2-adrenergic receptor. Phosphoamino acid analysis establishes that insulin receptor-catalyzed phosphorylation of the beta 2-adrenergic receptor in vitro is confined to phosphotyrosine. High pressure liquid chromatography and two-dimensional mapping reveal insulin receptor-catalyzed phosphorylation of the beta 2-adrenergic receptor at residues Tyr132/Tyr141, Tyr350/Tyr354, and Tyr364, known sites of phosphorylation in response to insulin in vivo. Insulin-like growth factor-I receptor as well as the insulin receptor displays the capacity to phosphorylate the beta 2-adrenergic receptor in vitro, establishing a new paradigm, i.e. G-protein-linked receptors acting as substrates for intrinsic tyrosine kinase growth factor receptors.</p>
dc.identifier.submissionpathoapubs/803
dc.contributor.departmentProgram in Molecular Medicine and the Department of Biochemistry and Molecular Biology
dc.source.pages1061-4


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