A novel catecholamine-activated adenosine cyclic 3',5'-phosphate independent pathway for .beta.-adrenergic receptor phosphorylation in wild-type and mutant S49 lymphoma cells: mechanism of homologous desensitization of adenylate cyclase
- 1 March 1986
- journal article
- research article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 25 (6) , 1371-1377
- https://doi.org/10.1021/bi00354a027
Abstract
Virtually all known biological actions stimulated by .beta.-adrenergic and other adenylate cyclase coupled receptors are mediated by cAMP-dependent protein kinase. Nonetheless, "homologous" or .beta.-adrenergic agonist-specific desensitization does not require cAMP. Since .beta.-adrenergic receptor phosphorylation may be involved in desensitization, we studied agonist-promoted receptor phosphorylation during homologous desensitization in wild-type S49 lymphoma cells (WT) and two mutants defective in the cAMP-dependent pathway of .beta.-agonist-stimulated protein phosphorylation (cyc- cannot generate cAMP in response to .beta.-adrenergic agonists; kin- lacks cAMP-dependent kinase). All three cell types demonstrate rapid, .beta.-adrenergic agonist-promoted, stoichiometric phosphorylation of the receptor which is clearly not cAMP mediated. The amino acid residue phosphorylated is solely serine. These data demonstrate, for the first time, that catecholamines can promote phosphorylation of a cellular protein (the .beta.-adrenergic receptor) via a cAMP-independent pathway. Moreover, the ability of cells with mutations in the adenylate cyclase-cAMP-dependent protein kinase pathway to both homologously desensitize and phosphorylate the .beta.-adrenergic receptors provides very strong support for the notion that receptor phosphorylation may indeed be central to the molecular mechanism of desensitization.This publication has 28 references indexed in Scilit:
- Genetic analysis of beta-adrenergic receptor internalization and down-regulation.Proceedings of the National Academy of Sciences, 1985
- Functional alteration of the beta-adrenergic receptor during desensitization of mammalian adenylate cyclase by beta-agonists.Proceedings of the National Academy of Sciences, 1984
- Rapid internalization of the transferrin receptor in K562 cells is triggered by ligand binding or treatment with a phorbol ester.Proceedings of the National Academy of Sciences, 1984
- Determination of the desensitization of β-adrenergic receptors by [3H]CGP-12177Biochemical Journal, 1983
- Catecholamine-induced desensitization of turkey erythrocyte adenylate cyclase is associated with phosphorylation of the beta-adrenergic receptor.Proceedings of the National Academy of Sciences, 1983
- Photoaffinity labeling of the beta-adrenergic receptor from cultured lymphoma cells with [125I]iodoazidobenzylpindolol: loss of the label with desensitization.Proceedings of the National Academy of Sciences, 1983
- Two-dimensional gel analysis of cyclic amp effects in cultured s49 mouse lymphoma cells: Protein modifications, inductions and repressionsCell, 1979
- Biologically active phorbol esters specifically alter affinity of epidermal growth factor membrane receptorsNature, 1979
- Reconstitution of catecholamine-sensitive adenylate cyclase activity: interactions of solubilized components with receptor-replete membranes.Proceedings of the National Academy of Sciences, 1977
- Mode of orthophosphate uptake and ATP labeling by mammalian cellsBiochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis, 1976