We show here using synchronized Swiss mouse 3T3 fibroblasts that p70 S6 kinase (p70) and mitogen-activated protein kinases (p42/p44) are not only activated at the G/G boundary, but also in cells progressing from M into G. p70 activity increases 20-fold in G cells released from G. Throughout G, S, and G it decreases constantly, so that during M phase low kinase activity is measured. The kinase is reactivated 10-fold when cells released from a nocodazole-induced metaphase block enter G of the next cell cycle. p42/p44 in G cells are activated transiently early in G and are reactivated late in mitosis after nocodazole release. p70activity is dependent on permanent signaling from growth factors at all stages of the cell cycle. Immunofluorescence studies showed that p70 and its isoform p85 become concentrated in localized spots in the nucleus at certain stages in the cell cycle. Cell cycle-dependent changes in p70 activity are associated with alterations in the phosphorylation state of the protein. However, examination of the regulation of a p70mutant in which the four carboxyl-terminal phosphorylation sites are changed to acidic amino acids suggests that a mechanism independent of these phosphorylation sites controls the activity of the enzyme during the cell cycle.

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