Cell
Volume 67, Issue 4, 15 November 1991, Pages 723-730
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Identification of a Gs activator region of the β2-adrenergic receptor that is autoregulated via protein kinase A-dependent phosphorylation

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Abstract

We have localized a G protein activator region of the human β2-adrenergic receptor to region βIII-2 (from Arg259 to Lys273). The synthetic βIII-2, corresponding to the C-terminal end of the third cytoplasmic loop, activates Gs at nanomolar concentrations and weakly activates Gi. βIII-2 activates adenylyl cyclase at nanomolar concentrations in wild-type S49 lymphoma membranes, but not in membranes of unc mutant S49 cells, in which Gs is uncoupled from β-adrenergic stimulation. Phosphorylation of βIII-2 by cAMP-dependent protein kinase A, which is involved in the desensitization of the β-adrenergic receptor from Gs, drastically reduces the effect of βIII-2 on Gs while potentiating its action on Gi, resulting in a total loss of adenylyl cyclase-stimulating activity. These findings indicate that this receptor sequence is a multipotential G protein activator whose G protein specificity is regulated by protein kinase A.

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