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Somatic genetic analysis of cyclic AMP action: Characterization of unresponsive mutants
Author(s) -
Bourne Henry R.,
Coffino Philip,
Tomkins Gordon M.
Publication year - 1975
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1040850313
Subject(s) - cholera toxin , phosphodiesterase , mutant , endogeny , intracellular , protein kinase a , cyclic nucleotide , adenosine , biology , cyclic nucleotide phosphodiesterase , somatic cell , cyclase , wild type , adenylate kinase , nucleotide , receptor , biochemistry , enzyme , endocrinology , gene
N 6 ,O 2′ ‐dibutyryl adenosine 3′,5′‐monophosphate kills cultured mouse lymphosarcoma cells, but not resistant mutants derived by a single‐step clonal selection. Resistant clones lack the cyclic AMP binding proteins present in wild type, cyclic AMP sensitive clones. Both endogenous cyclic AMP, accumulated in response to isoproterenol or cholera toxin, and exogenous dibutyryl cyclic AMP induce cyclic AMP phosphodiesterase, slow growth, and eventually kill wild type cells. In the resistant mutants, however, the endogenous and exogenous cyclic nucleotides appear to be completely inactive. These results indicate that an intracellular receptor for cyclic AMP, previously shown to be associated with a cyclic AMP‐dependent protein kinase, mediates cyclic AMP's regulation of growth and phosphodiesterase synthesis.