Phorbol-ester-induced phosphorylation of the β2-adrenergic receptor decreases its coupling to Gs

AbstractPhorbol-esters have been shown to modulated the β-adrenergie-stimulated adenylyl cyclase in a number of cell lines. Here, using site directed mutagenesis, we investigate the role of the β-adrenergic receptor phosphorylation by protein kinase C in this regulatory process. Mutation of the serine-261, -262, -344 and -345 of the β2-adrenergic receptor prevented the phorbol-ester-induced phosphorylation of the receptor. This mutation also abolished the phorbol-ester-induced decrease in high-affinity agonist binding and potency of the β2adrenergic receptor. We suggest that protein kinase C mediated phosphorylation of the receptor promotes its functional uncoupling