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Mitogenic and antimitogenic effects of cholera toxin-mediated cyclic AMP levels in 3T3 cells

✍ Scribed by Lou A. Smets; Henny Van Rooy


Publisher
John Wiley and Sons
Year
1987
Tongue
English
Weight
527 KB
Volume
133
Category
Article
ISSN
0021-9541

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✦ Synopsis


The effect of time-controlled exposures to cholera toxin (CT) on intracellular levels of cyclic AMP (CAMP) and on the proliferative response of serumstimulated 3T3 cells was investigated. Continuous exposure to CT caused up to 8-fold raises in cAMP content and inhibited DNA replication by delaying G1-S transition and by reducing the fraction of cells committed to DNA replication. In contrast, short exposures to CT during Go-G1 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 G1 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 acquisition of the state of competence by quiescent cells (Go-G1 transition) but antagonistic on the onset of DNA replication (G,-S transition) in committed cells. The observations reconcile a number of controversial conclusions regarding the role of cAMP in cell cycle control.


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