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Mitogenic and antimitogenic effects of cholera toxin‐mediated cyclic AMP levels in 3T3 cells
Author(s) -
Smets Lou A.,
Van Rooy Henny
Publication year - 1987
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.1041330227
Subject(s) - cholera toxin , dna synthesis , dna replication , intracellular , cell cycle , biology , dna , stimulation , cell , 3t3 cells , microbiology and biotechnology , cell culture , endocrinology , biochemistry , genetics , transfection
The effect of time‐controlled exposures to cholera toxin (CT) on intracellular levels of cyclic AMP (cAMP) and on the proliferative response of serum‐stimulated 3T3 cells was investigated. Continuous exposure to CT caused up to 8‐fold raises in cAMP content and inhibited DNA replication by delaying G 1 ‐S transition and by reducing the fraction of cells committed to DNA replication. In contrast, short exposures to CT during G 0 ‐G 1 transition increased the fraction of cells responding to serum stimulation and potentiated the serum‐induced morphological changes in the cell monolayer. A short exposure during late G 1 phase, however, inhibited the onset of DNA synthesis but had little effect on ongoing DNA replication. The results indicate that cAMP has diverse and opposite effects on two defined restriction points in cell cycle control. Cyclic AMP was positively involved in the acquistion of the state of competence by quiescent cells (G 0 ‐G 1 transition) but antagonistic on the onset of DNA replication (G 1 ‐S transition) in committed cells. The observations reconcile a number of controversial conclusions regarding the role of cAMP in cell cycle control.