The M phase kinase Greatwall (Gwl) promotes inactivation of PP2A/B55δ, a phosphatase directed against CDK phosphosites

PV Castilho, BC Williams, S Mochida… - Molecular biology of …, 2009 - Am Soc Cell Biol
PV Castilho, BC Williams, S Mochida, Y Zhao, ML Goldberg
Molecular biology of the cell, 2009Am Soc Cell Biol
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 B55δ regulatory subunit. Gwl is activated during M phase by Cdk1/cyclin B (MPF), but …
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 B55δ regulatory subunit. Gwl is activated during M phase by Cdk1/cyclin B (MPF), but once activated, Gwl promotes PP2A/B55δ inhibition with no further requirement for MPF. In the absence of Gwl, PP2A/B55δ remains active even when MPF levels are high. The removal of PP2A/B55δ 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.
Am Soc Cell Biol