The beta-adrenergic receptor is a substrate for the insulin receptor tyrosine kinase
Authors
Baltensperger, KurtKaroor, Vijaya
Paul, Hyacinth
Ruoho, Arnold E.
Czech, Michael P.
Malbon, Craig C.
UMass Chan Affiliations
Program in Molecular Medicine and the Department of Biochemistry and Molecular BiologyDocument Type
Journal ArticlePublication Date
1996-01-12Keywords
Amino Acid SequenceAnimals
CHO Cells
Cricetinae
GTP-Binding Proteins
Humans
Molecular Sequence Data
Phosphorylation
Receptor Protein-Tyrosine Kinases
Receptor, IGF Type 1
Receptor, Insulin
Receptors, Adrenergic, beta-2
Recombinant Proteins
Substrate Specificity
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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.Source
J Biol Chem. 1996 Jan 12;271(2):1061-4.
DOI
10.1074/jbc.271.2.1061Permanent Link to this Item
http://hdl.handle.net/20.500.14038/42456PubMed ID
8557631Related Resources
ae974a485f413a2113503eed53cd6c53
10.1074/jbc.271.2.1061
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