Insulin counterregulates catecholamine action at several levels, primarily in liver, fat, and adipose tissue. Herein we observe that expression of increased levels of β2-adrenergic receptor increasingly inhibits insulin-stimulated phosphorylation of its primary downstream substrates (IRS-1,2). In Chinese hamster ovary cells, the insulin receptor phosphorylates dominantly Tyr364 in the C-terminal cytoplasmic domain of the β-receptor. A Y364A mutant form of the β2-adrenergic, in contrast, loses it ability to inhibit insulin-stimulated phosphorylation of IRS-1,2. Upon phosphorylation, the C-terminal cytoplasmic domain of the β2-adrenergic receptor demonstrates a potent inhibitory feedback action that can block both insulin-stimulated autophosphorylation of the insulin receptor and phosphorylation of IRS-1,2 in NIH mouse 3T3-L1 adipocyte membranes. Studies in vitro with purified insulin receptor and the C-terminal cytoplasmic domain of the β2-adrenergic receptor demonstrate that the tyrosine-phosphorylated β-receptor domain is a potent counterregulatory inhibitor of the insulin receptor tyrosine kinase.
CITATION STYLE
Doronin, S., Wang, H. Y., & Malbon, C. C. (2002). Insulin stimulates phosphorylation of the β2-adrenergic receptor by the insulin receptor, creating a potent feedback inhibitor of its tyrosine kinase. Journal of Biological Chemistry, 277(12), 10698–10703. https://doi.org/10.1074/jbc.M109432200
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