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The beta-adrenergic receptor kinase: role in homologous desensitization in S49 lymphoma cells.

Publication ,  Journal Article
Strasser, RH; Benovic, JL; Lefkowitz, RJ; Caron, MG
Published in: Adv Exp Med Biol
1988

Phosphorylation of the beta-adrenergic receptor (beta AR) is closely associated with homologous desensitization of the beta-adrenergic receptor-coupled adenylate cyclase system. Homologous desensitization and receptor phosphorylation also occur in cell mutants which are deficient in their cAMP-dependent protein kinase (kin- mutant of S49 lymphoma cells). beta AR phosphorylation is mediated by a cAMP-independent protein kinase which phosphorylates the receptor only when it is occupied by a beta-agonist. During the time course of desensitization the beta AR kinase (beta ARK) activity is translocated from a cytoplasmic to a plasma membrane location. beta ARK translocation can also be effected by prostaglandin E1 (PGE1) suggesting that this beta ARK may represent a more general enzyme capable of phosphorylating other adenylate cyclase-coupled receptors. Thus, beta ARK may play a key role in the process of homologous desensitization of adenylate cyclase coupled receptors. Extracellular hormones interact with specific receptors at the outer surface of the plasma membrane and thus initiate a cellular response. One of the best studied transmembrane signalling systems known to be coupled to the occupancy of cell surface receptors is adenylate cyclase. The adenylate cyclase system is composed of various components all of which have been purified to homogeneity (Shorr et al., 1982; Homcy et al., 1983; Benovic et al., 1984; Codina et al., 1984; Northup et al., 1980; Sternweis et al., 1981; Bokoch et al., 1984; Pfeuffer et al., 1985). Initially, agonist binding to the receptor promotes coupling of the occupied receptor to one of the guanine nucleotide binding regulatory proteins. These proteins are members of a family of heterotrimeric proteins consisting of alpha, beta and gamma subunits. Stimulatory receptors like the beta-adrenergic (Cerione et al., 1984) or glucagon (Iyengar et al., 1979) receptors couple to the stimulatory regulatory protein Ns (or Gs) whereas inhibitory receptors like the alpha 2-adrenergic (Jacobs et al., 1976) or M2-muscarinic (Harden et al., 1982) receptors couple to the inhibitory regulatory protein Ni (or Gi). Prolonged exposure to agonist hormones, either stimulatory or inhibitory, results in an attenuation of the response to the hormonal activation, a phenomenon called tachyphylaxis or desensitization (Harden, 1983; Sibley and Lefkowitz, 1985; Sharma et al., 1975). One of the best studied models for desensitization is the beta-adrenergic receptor-coupled adenylate cyclase system. In this system two different forms of desensitization have been characterized.(ABSTRACT TRUNCATED AT 400 WORDS)

Duke Scholars

Published In

Adv Exp Med Biol

DOI

ISSN

0065-2598

Publication Date

1988

Volume

231

Start / End Page

503 / 517

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Receptors, Adrenergic, beta
  • Protein Processing, Post-Translational
  • Protein Kinases
  • Phosphorylation
  • Mice
  • Lymphoma
  • Kinetics
  • Isoproterenol
  • General & Internal Medicine
 

Citation

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Strasser, R. H., Benovic, J. L., Lefkowitz, R. J., & Caron, M. G. (1988). The beta-adrenergic receptor kinase: role in homologous desensitization in S49 lymphoma cells. Adv Exp Med Biol, 231, 503–517. https://doi.org/10.1007/978-1-4684-9042-8_43
Strasser, R. H., J. L. Benovic, R. J. Lefkowitz, and M. G. Caron. “The beta-adrenergic receptor kinase: role in homologous desensitization in S49 lymphoma cells.Adv Exp Med Biol 231 (1988): 503–17. https://doi.org/10.1007/978-1-4684-9042-8_43.
Strasser RH, Benovic JL, Lefkowitz RJ, Caron MG. The beta-adrenergic receptor kinase: role in homologous desensitization in S49 lymphoma cells. Adv Exp Med Biol. 1988;231:503–17.
Strasser, R. H., et al. “The beta-adrenergic receptor kinase: role in homologous desensitization in S49 lymphoma cells.Adv Exp Med Biol, vol. 231, 1988, pp. 503–17. Pubmed, doi:10.1007/978-1-4684-9042-8_43.
Strasser RH, Benovic JL, Lefkowitz RJ, Caron MG. The beta-adrenergic receptor kinase: role in homologous desensitization in S49 lymphoma cells. Adv Exp Med Biol. 1988;231:503–517.

Published In

Adv Exp Med Biol

DOI

ISSN

0065-2598

Publication Date

1988

Volume

231

Start / End Page

503 / 517

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Receptors, Adrenergic, beta
  • Protein Processing, Post-Translational
  • Protein Kinases
  • Phosphorylation
  • Mice
  • Lymphoma
  • Kinetics
  • Isoproterenol
  • General & Internal Medicine