Greatwall Phosphorylates an Inhibitor of Protein Phosphatase 2Α That Is Essential for Mitosis

@article{Mochida2010GreatwallPA,
  title={Greatwall Phosphorylates an Inhibitor of Protein Phosphatase 2Α That Is Essential for Mitosis},
  author={Satoru Mochida and Sarah L. Maslen and Mark Skehel and Timothy Hunt},
  journal={Science},
  year={2010},
  volume={330},
  pages={1670 - 1673}
}
Beyond the Greatwall Protein phosphorylation and dephosphorylation provide a central mechanism that controls the eukaryotic cell division cycle and entry of cells into mitosis. A form of protein phosphatase 2A (PP2A) has an important role inhibiting phosphorylation-dependent activation of cyclin-dependent kinase 1 (CDK1) itself and also dephosphorylating substrates of the active CDK1 that promote mitosis. PP2A activity is inhibited when another protein kinase, known as Greatwall, is activated… 
Regulating Greatwall for mitosis
TLDR
In search for new regulators of Xenopus Gwl (xGwl), the authors analyzed the co-immunoprecipitation complex of this kinase from Xenopus oocytes, and identified importin α/β and chaperone complex Hsp90/Cdc37 as xGwl binding partners and identified a dynamic nucleocytoplasmic localization of Gwl during the cell cycle in Xenopus S3 cells.
Greatwall dephosphorylation and inactivation upon mitotic exit is triggered by PP1
TLDR
PP1 triggers Gwl inactivation upon meiotic and mitotic exit by targeting dephosphorylation of this kinase on its Ser875 activating residue, and it is shown that when PP2A-B55 is fully reactivated by depleting Arpp19, this protein phosphatase is able to deph phosphorylate both activating sites, even in the absence of PP1.
The Greatwall-PP2A axis in cell cycle control.
TLDR
The importance of spatiotemporal regulation of Gwl, endosulfines, and PP2A-B55 for cell cycle progression, which regulates gene expression in yeast, and this function could be conserved in metazoans, is shown.
Spatial regulation of greatwall by Cdk1 and PP2A-Tws in the cell cycle
TLDR
The results indicate that the cyclic changes in Gwl localization at mitotic entry and exit are directly regulated by the antagonistic cyclin B-Cdk1 and PP2A-Tws enzymes.
Greatwall-Endosulfine: A Molecular Switch that Regulates PP2A/B55 Protein Phosphatase Activity in Dividing and Quiescent Cells
TLDR
The current knowledge of the Greatwall-ENSA-PP2A/B55 pathway is reviewed and its role in cell cycle progression and as an integrator of nutritional cues is discussed.
Greatwall kinase at a glance
TLDR
How Gwl is regulated in space and time, and how the Gwl–Arpp19–ENSA–PP2A-B55 pathway plays an essential role in the control of M and S phases from yeast to human are discussed are discussed.
The master Greatwall kinase, a critical regulator of mitosis and meiosis.
TLDR
New data showing that in addition to the Cdk1-cyclin B complex, Greatwall (Gwl) kinase is also required to enter into and maintain mitosis support the idea that the Gwl-Arpp19/ENSA-PP2A-B55 pathway is essential to achieve an efficient division of cells and to maintain genomic stability.
On the regulation of protein phosphatase 2A and its role in controlling entry into and exit from mitosis.
  • T. Hunt
  • Biology
    Advances in biological regulation
  • 2013
The overlooked greatwall: a new perspective on mitotic control
TLDR
The genetic and biochemical evidence for Greatwall kinase and its substrate Endosulphine are reviewed as the key components of this previously obscure regulatory network that facilitates Cdk1-CycB activity by inhibiting the form of protein phosphatase 2A having a B55 regulatory subunit (PP2A-B55).
The Greatwall kinase: a new pathway in the control of the cell cycle
TLDR
New data in yeast support the view that Gwl, Arpp19 and ENSA could function as the core of a new signalization pathway that, by targeting different final substrates, could participate in a variety of physiological functions.
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References

SHOWING 1-10 OF 30 REFERENCES
Regulation of Mih1/Cdc25 by protein phosphatase 2A and casein kinase 1
TLDR
The function and regulation of Mih1, the budding yeast homologue of Cdc25, are characterized and it is found that Mih2 is hyperphosphorylated early in the cell cycle and is dephosphored as cells enter mitosis, suggesting that Mh1 regulation is achieved by a balance of opposing kinase and phosphatase activities.
PP1-mediated dephosphorylation of phosphoproteins at mitotic exit is controlled by inhibitor-1 and PP1 phosphorylation
TLDR
It is reported here that protein phosphatase-1 (PP1) is the main catalyst of mitotic phosphoprotein dephosphorylation, and Cdc2 both phosphorylates multiple mitotic substrates and inhibits their PP1-mediated deph phosphorylation.
Greatwall maintains mitosis through regulation of PP2A
TLDR
It is shown that GW depletion promotes mitotic exit, even in the presence of a high cyclin B–Cdc2 activity by inducing dephosphorylation of mitotic substrates, and suggests that mitotic entry and maintenance is not only mediated by the activation of cyclinB–CDC2 but also by the regulation of PP2A by GW.
Regulated activity of PP2A–B55δ is crucial for controlling entry into and exit from mitosis in Xenopus egg extracts
TLDR
It is found that PP2A associated with a B55δ subunit is relatively specific for a model mitotic CDK substrate in Xenopus egg extracts and seems to be a key regulator of entry into and exit from mitosis.
The M phase kinase Greatwall (Gwl) promotes inactivation of PP2A/B55delta, a phosphatase directed against CDK phosphosites.
TLDR
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 is supported.
Cell cycle regulation of a Xenopus Wee1-like kinase.
TLDR
These studies indicate that the down-regulation of Wee1-like kinase activity at mitosis is a multistep process that occurs after other biochemical reactions have signaled the successful completion of S phase.
Loss of human Greatwall results in G2 arrest and multiple mitotic defects due to deregulation of the cyclin B-Cdc2/PP2A balance
TLDR
It is shown that the functional human ortholog of Greatwall protein kinase (Gwl) is the microtubule-associated serine/threonine kinase-like protein, MAST-L, and that Gwl is crucial for mediating this regulation in somatic human cells.
...
1
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3
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