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The 15-amino acid motif of the C terminus of the beta2-adrenergic receptor is sufficient to confer insulin-stimulated counterregulation to the beta1-adrenergic receptor

The 15-amino acid motif of the C terminus of the beta2-adrenergic receptor is sufficient to confer insulin-stimulated counterregulation to the beta1-adrenergic receptor

Endocrinology 146(1): 450-457

Insulin counterregulates catecholamine action in part by inducing the sequestration of beta2-adrenergic receptors. Although similar to agonist-induced sequestration, insulin-induced internalization of beta2-adrenergic receptors operates through a distinct and better-understood cellular pathway. The effects of insulin treatment on the function and trafficking of both beta1- and beta2-adrenergic receptors were tested. The beta2-adrenergic receptors were counterregulated and internalized in response to insulin. The beta1-adrenergic receptors, in sharp contrast, are shown to be resistant to the ability of insulin to counterregulate function and induce receptor internalization. Using chimeric receptors composed of beta1-/beta2-adrenergic receptors in tandem with mutagenesis, we explored the role of the C-terminal cytoplasmic tail of the beta2-adrenergic receptors for insulin-induced counterregulation. Substitution of the C-terminal cytoplasmic tail of the beta2-adrenergic receptor on the beta1-adrenergic receptor enabled the chimeric G protein-coupled receptor to be functionally and spatially regulated by insulin. Truncation of the beta2-adrenergic receptor C-terminal cytoplasmic tail to a 15-amino acid motif harboring a potential Src homology 2-binding domain at Y350 and an Akt phosphorylation site at S345,346 was sufficient to enable receptor regulation by insulin.

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Accession: 050519544

Download citation: RISBibTeXText

PMID: 15388645

DOI: 10.1210/en.2004-0595

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