Roles of Greatwall kinase in the regulation of cdc25 phosphatase.
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. 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, or in the presence of an activator of protein kinase A 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.
Zhao
Yong
Y
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853-2703, USA.
Haccard
Olivier
O
Wang
Ruoning
R
Yu
Jiangtao
J
Kuang
Jian
J
Jessus
Catherine
C
Goldberg
Michael L
ML
D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System; D009865:Oocytes / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000737:chemistry; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis; D020687:cdc25 Phosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D017346:Protein Serine-Threonine Kinases; D011994:Recombinant Proteins; D012694:Serine; D029867:Xenopus Proteins; D020687:cdc25 Phosphatases; C490167:Gwl protein, Drosophila; C101085:Plk1 protein, Xenopus; D000097869:Polo-Like Kinase 1