A Role for cAMP-Dependent Protein Kinase in Early Embryonic Divisions

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 21; pp. 9896 - 9900
• Main Authors: Grieco, Domenico, Avvedimento, Enrico V., Gottesman, Max E.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 11.10.1994; National Acad Sciences; National Academy of Sciences
• Subjects: 8-Bromo Cyclic Adenosine Monophosphate - pharmacology; Animals; Biochemistry; CDC2 Protein Kinase - isolation & purification; CDC2 Protein Kinase - metabolism; cdc25 Phosphatases; Cell cycle; Cell Cycle - physiology; Cell cycle proteins; Cell division; Cell Division - physiology; Chromatography, Affinity; Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors; Cyclic AMP-Dependent Protein Kinases - metabolism; Cyclins; Cyclins - isolation & purification; Cyclins - metabolism; Cycloheximide - pharmacology; Eggs; Embryo, Nonmammalian - cytology; Embryo, Nonmammalian - physiology; Ethers, Cyclic - pharmacology; Female; Freshwater; Histones; Immunoblotting; Interphase; Macromolecular Substances; Maturation-Promoting Factor - metabolism; Metaphase; Mitosis; Okadaic Acid; Oocytes - cytology; Oocytes - enzymology; Phosphatases; Phosphoprotein Phosphatases - metabolism; Phosphorylation; Proteins; Proteins - metabolism; Recombinant Fusion Proteins - metabolism; Sea Urchins; Time Factors; Xenopus
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.21.9896

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 p34cdc2remains tyrosine-phosphorylated. PKA appears to stimulate an okadaic acid-sensitive serine/threonine phosphatase that acts upon cdc25. In this way PKA could downregulate the p34cdc2tyrosine phosphatase activity of cdc25 and consequently block the activation of the M-phase-promoting factor.