Abstract
We have previously shown that Greatwall kinase (Gwl) is required for M phase entry and maintenance in Xenopus egg extracts. Here, we demonstrate that Gwl plays a crucial role in a novel biochemical pathway that inactivates, specifically during M phase, "antimitotic" phosphatases directed against phosphorylations catalyzed by cyclin-dependent kinases (CDKs). A major component of this phosphatase activity is heterotrimeric PP2A containing the B55delta regulatory subunit. Gwl is activated during M phase by Cdk1/cyclin B (MPF), but once activated, Gwl promotes PP2A/B55delta inhibition with no further requirement for MPF. In the absence of Gwl, PP2A/B55delta remains active even when MPF levels are high. The removal of PP2A/B55delta corrects the inability of Gwl-depleted extracts to enter M phase. These findings support the hypothesis that M phase requires not only high levels of MPF function, but also the suppression, through a Gwl-dependent mechanism, of phosphatase(s) that would otherwise remove MPF-driven phosphorylations.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Calcineurin / metabolism
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Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
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Cell Division / physiology*
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Cyclin-Dependent Kinases / metabolism*
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Enzyme Inhibitors / pharmacology
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Maturation-Promoting Factor / genetics
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Maturation-Promoting Factor / metabolism
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Okadaic Acid / pharmacology
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Oocytes / cytology
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Oocytes / drug effects
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Oocytes / metabolism
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Phosphorylation
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Protein Phosphatase 2 / antagonists & inhibitors
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Protein Phosphatase 2 / genetics
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Protein Phosphatase 2 / metabolism*
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Protein Subunits / genetics
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Protein Subunits / metabolism
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Xenopus Proteins / genetics
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Xenopus Proteins / metabolism*
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Xenopus laevis
Substances
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Enzyme Inhibitors
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Protein Subunits
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Xenopus Proteins
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Okadaic Acid
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MASTL protein, Xenopus
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Protein Serine-Threonine Kinases
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Cyclin-Dependent Kinases
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Maturation-Promoting Factor
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Calcineurin
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Protein Phosphatase 2