Open AccessAdenylate cyclase permanently uncoupled from hormone receptors in a novel variant of S49 mouse lymphoma cells.
Author(s) -
Tatsuya Haga,
Elliott M. Ross,
Hannah Anderson,
Alfred G. Gilman
Publication year - 1977
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.74.5.2016
Subject(s) - cyclase , adenylate kinase , cholera toxin , receptor , growth hormone releasing hormone receptor , phosphodiesterase , biology , chemistry , biochemistry , medicine , endocrinology , hormone receptor , enzyme , genetics , cancer , breast cancer
A novel variant of the S49 mouse lymphoma has been selected from wild-type cells by growth in medium containing the beta-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 beta-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 (cyclizine), 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 beta-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 methanisms of transmission of information from hormone receptors to adenylate cyclase.