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Somatic genetic analysis of cyclic AMP action: Selection of unresponsive mutants
Author(s) -
Coffino Philip,
Bourne Henry R.,
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.1040850312
Subject(s) - somatic cell , mutant , protein kinase a , biology , mutation , protein subunit , cytolysis , ploidy , cytoplasm , microbiology and biotechnology , kinase , genetics , biochemistry , gene , in vitro , cytotoxicity
Dibutyryl cyclic AMP and theophylline kill S49.1 mouse lymphoma tissue culture cells. When cells are grown in soft agar with these drugs, the few clones that survive are resistant to cytolysis. The rate of mutation to resistance is 1–3 × 10 −7 /cell/generation in both diploid and tetraploid cells. The incidence of mutants is increased by treatment with a chemical mutagen ICR 191. The mutation is consistently associated with greatly reduced or absent cytoplasmic cyclic AMP binding protein. These results suggest that a somatic mutation leads to a defect of the protein kinase regulatory subunit and that activity of this kinase is required for induction of cell death by cyclic AMP.