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Proc Natl Acad Sci U S A
1994 Oct 11;9121:9896-900. doi: 10.1073/pnas.91.21.9896.
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A role for cAMP-dependent protein kinase in early embryonic divisions.
Grieco D
,
Avvedimento EV
,
Gottesman ME
.
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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 p34cdc2, but the resultant complex lacks kinase activity and p34cdc2 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 p34cdc2 tyrosine phosphatase activity of cdc25 and consequently block the activation of the M-phase-promoting factor.