A ROLE FOR CAMP-DEPENDENT PROTEIN-KINASE IN EARLY EMBRYONIC DIVISIONS

The cAMP-dependent protein kinase (PKA) pathway affects cell cycle progression in ''cycling'' Xenopus egg extracts. The concentration of free PKA catalytic subunit oscillates during the cell cycle with a peak at the mitosis-interphase transition and a minimum at the onset of mitosis. Inhibition of endogenous PKA in interphase hastens the onset of mitosis. Stimulation of PKA induces interphase arrest, preventing the activation of the M-phase-promoting factor. PKA does not block the accumulation of cyclin or its binding to p34(cdc2), but the resultant complex lacks kinase activity and p34(cdc2) remains tyrosine-phosphorylated. PKA appears to stimulate an okadaic acid-sensitive serine/threonine phosphatase that acts upon cdc25. In this way PKA could downregulate the p34(cdc2) tyrosine phosphatase activity of cdc25 and consequently block the activation of the M-phase-promoting factor.