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PMID: 7937913 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A role for cAMP-dependent protein kinase in early embryonic divisions.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 91 ·No. 21 ·1994-10-11 ·Pages 9896-900

Grieco D, Avvedimento EV, Gottesman ME

Abstract

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.

MeSH Terms
8-Bromo Cyclic Adenosine Monophosphate/pharmacology Animals CDC2 Protein Kinase/isolation & purification,metabolism Cell Cycle/physiology Cell Division/physiology Chromatography, Affinity Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors,metabolism Cyclins/isolation & purification,metabolism Cycloheximide/pharmacology Embryo, Nonmammalian/cytology,physiology Ethers, Cyclic/pharmacology Female Immunoblotting Interphase Macromolecular Substances Maturation-Promoting Factor/metabolism Mitosis Okadaic Acid Oocytes/cytology,enzymology Phosphoprotein Phosphatases/metabolism Proteins/metabolism Recombinant Fusion Proteins/metabolism Sea Urchins Time Factors Xenopus cdc25 Phosphatases
Chemicals
Cyclins Ethers, Cyclic Macromolecular Substances Proteins Recombinant Fusion Proteins Okadaic Acid 8-Bromo Cyclic Adenosine Monophosphate Cycloheximide Cyclic AMP-Dependent Protein Kinases CDC2 Protein Kinase Maturation-Promoting Factor Phosphoprotein Phosphatases cdc25 Phosphatases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Grieco D
Institute of Cancer Research, Columbia University, New York, NY 10032.
Avvedimento E V
Gottesman M E
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.91.21.9896
Published
1994-10-11
Pages
9896-900
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC44924
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.91.21.9896 PMC Full Text View journal details
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