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 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.
Grieco
D
D
Institute of Cancer Research, Columbia University, New York, NY 10032.
Avvedimento
E V
EV
Gottesman
M E
ME
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D016203:CDC2 Protein Kinase / Q000302:isolation & purification / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D002846:Chromatography, Affinity; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016213:Cyclins / Q000302:isolation & purification / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology; D004988:Ethers, Cyclic / Q000494:pharmacology; D005260:Female; D015151:Immunoblotting; D007399:Interphase; D046911:Macromolecular Substances; D016200:Maturation-Promoting Factor / Q000378:metabolism; D008938:Mitosis; D019319:Okadaic Acid; D009865:Oocytes / Q000166:cytology* / Q000201:enzymology*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012617:Sea Urchins; D013997:Time Factors; D014981:Xenopus; D020687:cdc25 Phosphatases
D016213:Cyclins; D004988:Ethers, Cyclic; D046911:Macromolecular Substances; D011506:Proteins; D011993:Recombinant Fusion Proteins; D019319:Okadaic Acid; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003513:Cycloheximide; D017868:Cyclic AMP-Dependent Protein Kinases; D016203:CDC2 Protein Kinase; D016200:Maturation-Promoting Factor; D010749:Phosphoprotein Phosphatases; D020687:cdc25 Phosphatases