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MBC in Press, published online ahead of print January 16, 2008
Mol. Biol. Cell 10.1091/mbc.E07-11-1099

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Submitted on November 2, 2007
Revised on December 26, 2007
Accepted on January 8, 2008

Roles of Greatwall Kinase in the Regulation of Cdc25 Phosphatase

Yong Zhao,* Olivier Haccard,{dagger} Ruoning Wang,{ddagger} Jiangtao Yu,* Jian Kuang,{ddagger} Catherine Jessus,{dagger} and Michael L. Goldberg*

*Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853-2703; {dagger}Centre Nationale de la Recherche Scientifique (CNRS), UMR7622, Université Pierre et Marie Curie, Biologie du Développement, 75252 Paris, FRANCE; {ddagger}Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030

Monitoring Editor: Mark Solomon

We previously reported that immunodepletion of Greatwall kinase prevents Xenopus egg extracts from entering or maintaining M phase due to the accumulation of inhibitory phosphorylations on Thr14 and Tyr15 of Cdc2. M phase promoting factor (MPF) in turn activates Greatwall, implying that Greatwall participates in an MPF autoregulatory loop (Yu et al., 2006). We show here that activated Greatwall both accelerates the mitotic G2/M transition in cycling egg extracts and induces meiotic maturation in G2-arrested Xenopus oocytes in the absence of progesterone. Activated Greatwall can induce phosphorylations of Cdc25 in the absence of the activity of Cdc2, Plx1 (Xenopus Polo-like kinase) or mitogen-activated protein kinase (MAPK), or in the presence of an activator of protein kinase A (PKA) that normally blocks mitotic entry. The effects of active Greatwall mimic in many respects those associated with addition of the phosphatase inhibitor okadaic acid (OA); moreover, OA allows cycling extracts to enter M phase in the absence of Greatwall. Taken together, these findings support a model in which Greatwall negatively regulates a crucial phosphatase that inhibits Cdc25 activation and M phase induction.


Address correspondence to: Michael L. Goldberg (mlg11{at}cornell.edu)




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P. V. Castilho, B. C. Williams, S. Mochida, Y. Zhao, and M. L. Goldberg
The M Phase Kinase Greatwall (Gwl) Promotes Inactivation of PP2A/B55{delta}, a Phosphatase Directed Against CDK Phosphosites
Mol. Biol. Cell, November 15, 2009; 20(22): 4777 - 4789.
[Abstract] [Full Text] [PDF]




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