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Regulation of adrenergic receptor function by phosphorylation ii. effects of agonist occupancy on phosphorylation of alpha 1 and beta 2 adrenergic receptors by protein kinase c and the cyclic amp dependent protein kinase



Regulation of adrenergic receptor function by phosphorylation ii. effects of agonist occupancy on phosphorylation of alpha 1 and beta 2 adrenergic receptors by protein kinase c and the cyclic amp dependent protein kinase



Journal of Biological Chemistry 262(7): 3106-3113



The present study was undertaken to determine the ability of protein kinase C and protein kinase A to directly phosphorylate the purified .alpha.1-and .beta.2-adrenergic receptors (AR). Both the catalytic subunit of protein kinase A and the protein kinase C, purified from bovine heart and pig brain, respectively, are able to phosphorylate the purified .alpha.1-AR from DDT1 MF-2 smooth muscle cells. Occupancy of the receptor by an .alpha.1 agonist, norepinephrine (100 .mu.M), increases the rate of phosphorylation by protein kinase C but not by protein kinase A. The maximum stoichiometry of phosphorylation obtained is not affected by the agonist and reached 3 mol of PO4/mol of receptor for protein kinase C and 1 mol of PO4/mol of receptor for protein kinase A. The phosphopeptide maps of the trypsinized .alpha.1-AR phosphorylated by each kinase differ drastically. The .beta.2-AR purified from hamster lungs can also be phosphorylated by the two kinases. In contrast to the .alpha.1-AR, the occupancy of the .beta.2-AR by the agonist isoproterenol (20 .mu.M) increases the rate of phosphorylation of the .beta.2-AR by protein kinase A but not by protein kinase C. The maximum amount of phosphate incorporated into the receptor is not affected in either case by the agonist and reaches 1 mol of PO4/mol of receptor with protein kinase A and 0.4 mol of PO4/mol of receptor with protein kinase C. The phosphopeptide maps of the trypsinized receptor phosphorylated by either kinase reveal similar profiles. Thus, both .alpha.1 -AR and .beta.2-AR are substrates for protein kinase A and protein kinase C. Agonist occupancy of the two receptors facilitates their phosphorylation only by the protein kinase coupled to their own signal transduction pathway. These observations sugest that "feedback" and "cross-system" phosphorylation may represent distinct and differently regulated mechanisms of modulation of receptor function.

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Accession: 006286378

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PMID: 3029101


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