The M phase kinase Greatwall (Gwl) promotes inactivation of PP2A/B55delta, a phosphatase directed against CDK phosphosites.
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.
Castilho
Priscila V
PV
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Williams
Byron C
BC
Mochida
Satoru
S
Zhao
Yong
Y
Goldberg
Michael L
ML
D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002455:Cell Division / Q000502:physiology*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016200:Maturation-Promoting Factor / Q000235:genetics / Q000378:metabolism; D019319:Okadaic Acid / Q000494:pharmacology; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
D004791:Enzyme Inhibitors; D021122:Protein Subunits; D029867:Xenopus Proteins; D019319:Okadaic Acid; C544010:MASTL protein, Xenopus; D017346:Protein Serine-Threonine Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D018844:Cyclin-Dependent Kinases; D016200:Maturation-Promoting Factor; D019703:Calcineurin; D054648:Protein Phosphatase 2