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Greatwall Phosphorylates an Inhibitor of Protein Phosphatase 2A That Is Essential for Mitosis
Satoru Mochida,1,2
Sarah L. Maslen,1
Mark Skehel,1
Tim Hunt1,*
Abstract:
Entry into mitosis in eukaryotes requires the activity of cyclin-dependentkinase 1 (Cdk1). Cdk1 is opposed by protein phosphatases intwo ways: They inhibit activation of Cdk1 by dephosphorylatingthe protein kinases Wee1 and Myt1 and the protein phosphataseCdc25 (key regulators of Cdk1), and they also antagonize Cdk1’sown phosphorylation of downstream targets. A particular formof protein phosphatase 2A (PP2A) containing a B55 subunit (PP2A-B55) is the major protein phosphatase that acts on model CDKsubstrates in Xenopus egg extracts and has antimitotic activity.The activity of PP2A-B55 is high in interphase and low in mitosis,exactly opposite that of Cdk1. We report that inhibition ofPP2A-B55 results from a small protein, known as -endosulfine(Ensa), that is phosphorylated in mitosis by the protein kinaseGreatwall (Gwl). This converts Ensa into a potent and specificinhibitor of PP2A-B55. This pathway represents a previouslyunknown element in the control of mitosis.
1 Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK. 2 Priority Organization for Innovation and Excellence, Kumamoto University, 2-2-1 Honjo, Kumamoto, Kumamoto 860-0811, Japan.
* To whom correspondence should be addressed. E-mail: tim.hunt{at}cancer.org.uk
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subunit (PP2A- B55
-endosulfine (Ensa), that is phosphorylated in mitosis by the protein kinase Greatwall (Gwl). This converts Ensa into a potent and specific inhibitor of PP2A-B55
