Adenylate cyclase permanently uncoupled from hormone receptors in a novel variant of S49 mouse lymphoma cells

T. Haga, E. M. Ross, H. J. Anderson, A. G. Gilman

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

A novel variant of the S49 mouse lymphoma has been selected from wild-type cells by growth in medium containing the β-adrenergic agonist terbutaline and inhibitors of cyclic nucleotide phosphodiesterase. In contrast to the situation in the wild-type clone, synthesis of adenosine 3':5'-monophosphate (cyclic AMP) is not stimulated by β-adrenergic agonists or by prostaglandin E1 either in intact variant cells or in membrane preparations of such clones. However, basal and NaF-stimulated activities of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] are normal, enzyme activity is stimulated by guanyl-5'-yl imidodiphosphate [Gpp(NH)p], and intact cells accumulate cyclic AMP when exposed to cholera toxin. Furthermore, variant cell membranes possess ligand-binding activity consistent with the conclusion that a normal or an excessive number of β-adrenergic receptors is present. Thus, interaction between the hormone-binding and the catalytic moieties of the adenylate cyclase system is lost. This variant phenotype, designated as uncoupled (UNC), has been stable for more than 100 generations without exposure to the drugs used for selection. Such cells should be useful for the elucidation of mechanisms of transmission of information from hormone receptors to adenylate cyclase.

Original languageEnglish (US)
Pages (from-to)2016-2020
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume74
Issue number5
StatePublished - 1977

Fingerprint

Adenylyl Cyclases
Lymphoma
Hormones
Guanylyl Imidodiphosphate
Adrenergic Agonists
Cyclic AMP
Clone Cells
Terbutaline
Alprostadil
Cholera Toxin
Cyclic Nucleotides
Phosphoric Diester Hydrolases
Adenosine
Adrenergic Receptors
Cell Membrane
Ligands
Phenotype
Membranes
Enzymes
Growth

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Adenylate cyclase permanently uncoupled from hormone receptors in a novel variant of S49 mouse lymphoma cells. / Haga, T.; Ross, E. M.; Anderson, H. J.; Gilman, A. G.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 74, No. 5, 1977, p. 2016-2020.

Research output: Contribution to journalArticle

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