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Mol Biol Cell
2001 Mar 01;123:551-63. doi: 10.1091/mbc.12.3.551.
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Positive regulation of Wee1 by Chk1 and 14-3-3 proteins.
Lee J
,
Kumagai A
,
Dunphy WG
.
???displayArticle.abstract??? Wee1 inactivates the Cdc2-cyclin B complex during interphase by phosphorylating Cdc2 on Tyr-15. The activity of Wee1 is highly regulated during the cell cycle. In frog egg extracts, it has been established previously that Xenopus Wee1 (Xwee1) is present in a hypophosphorylated, active form during interphase and undergoes down-regulation by extensive phosphorylation at M-phase. We report that Xwee1 is also regulated by association with 14-3-3 proteins. Binding of 14-3-3 to Xwee1 occurs during interphase, but not M-phase, and requires phosphorylation of Xwee1 on Ser-549. A mutant of Xwee1 (S549A) that cannot bind 14-3-3 is substantially less active than wild-type Xwee1 in its ability to phosphorylate Cdc2. This mutation also affects the intranuclear distribution of Xwee1. In cell-free kinase assays, Xchk1 phosphorylates Xwee1 on Ser-549. The results of experiments in which Xwee1, Xchk1, or both were immunodepleted from Xenopus egg extracts suggested that these two enzymes are involved in a common pathway in the DNA replication checkpoint response. Replacement of endogenous Xwee1 with recombinant Xwee1-S549A in egg extracts attenuated the cell cycle delay induced by addition of excess recombinant Xchk1. Taken together, these results suggest that Xchk1 and 14-3-3 proteins act together as positive regulators of Xwee1.
Aligue,
Regulation of Schizosaccharomyces pombe Wee1 tyrosine kinase.
1997, Pubmed
Aligue,
Regulation of Schizosaccharomyces pombe Wee1 tyrosine kinase.
1997,
Pubmed
Baber-Furnari,
Regulation of mitotic inhibitor Mik1 helps to enforce the DNA damage checkpoint.
2000,
Pubmed
Blasina,
A human homologue of the checkpoint kinase Cds1 directly inhibits Cdc25 phosphatase.
1999,
Pubmed
Boddy,
Replication checkpoint enforced by kinases Cds1 and Chk1.
1998,
Pubmed
Boyle,
Phosphopeptide mapping and phosphoamino acid analysis by two-dimensional separation on thin-layer cellulose plates.
1991,
Pubmed
Brown,
A human Cds1-related kinase that functions downstream of ATM protein in the cellular response to DNA damage.
1999,
Pubmed
Chan,
14-3-3Sigma is required to prevent mitotic catastrophe after DNA damage.
1999,
Pubmed
Christensen,
Mik1 levels accumulate in S phase and may mediate an intrinsic link between S phase and mitosis.
2000,
Pubmed
Coleman,
Cdc2 regulatory factors.
1994,
Pubmed
Dalal,
Cytoplasmic localization of human cdc25C during interphase requires an intact 14-3-3 binding site.
1999,
Pubmed
Dunphy,
The cdc25 protein contains an intrinsic phosphatase activity.
1991,
Pubmed
Elledge,
Cell cycle checkpoints: preventing an identity crisis.
1996,
Pubmed
Featherstone,
Fission yeast p107wee1 mitotic inhibitor is a tyrosine/serine kinase.
1991,
Pubmed
Gautier,
cdc25 is a specific tyrosine phosphatase that directly activates p34cdc2.
1991,
Pubmed
,
Xenbase
Guo,
Response of Xenopus Cds1 in cell-free extracts to DNA templates with double-stranded ends.
2000,
Pubmed
,
Xenbase
Honda,
14-3-3 zeta protein binds to the carboxyl half of mouse wee1 kinase.
1997,
Pubmed
Izumi,
Periodic changes in phosphorylation of the Xenopus cdc25 phosphatase regulate its activity.
1992,
Pubmed
,
Xenbase
Kumagai,
Regulation of Xenopus Cdc25 protein.
1997,
Pubmed
,
Xenbase
Kumagai,
14-3-3 proteins act as negative regulators of the mitotic inducer Cdc25 in Xenopus egg extracts.
1998,
Pubmed
,
Xenbase
Kumagai,
The Xenopus Chk1 protein kinase mediates a caffeine-sensitive pathway of checkpoint control in cell-free extracts.
1998,
Pubmed
,
Xenbase
Kumagai,
Binding of 14-3-3 proteins and nuclear export control the intracellular localization of the mitotic inducer Cdc25.
1999,
Pubmed
,
Xenbase
Kumagai,
Claspin, a novel protein required for the activation of Chk1 during a DNA replication checkpoint response in Xenopus egg extracts.
2000,
Pubmed
,
Xenbase
Kumagai,
Regulation of the cdc25 protein during the cell cycle in Xenopus extracts.
1992,
Pubmed
,
Xenbase
Kumagai,
Control of the Cdc2/cyclin B complex in Xenopus egg extracts arrested at a G2/M checkpoint with DNA synthesis inhibitors.
1995,
Pubmed
,
Xenbase
Lew,
Cell-cycle checkpoints that ensure coordination between nuclear and cytoplasmic events in Saccharomyces cerevisiae.
2000,
Pubmed
Lopez-Girona,
Nuclear localization of Cdc25 is regulated by DNA damage and a 14-3-3 protein.
1999,
Pubmed
Matsuoka,
Linkage of ATM to cell cycle regulation by the Chk2 protein kinase.
1998,
Pubmed
McGowan,
Cell cycle regulation of human WEE1.
1995,
Pubmed
Michael,
Coupling of mitosis to the completion of S phase through Cdc34-mediated degradation of Wee1.
1998,
Pubmed
,
Xenbase
Morgan,
Cyclin-dependent kinases: engines, clocks, and microprocessors.
1997,
Pubmed
Mueller,
Cell cycle regulation of a Xenopus Wee1-like kinase.
1995,
Pubmed
,
Xenbase
Mueller,
Myt1: a membrane-associated inhibitory kinase that phosphorylates Cdc2 on both threonine-14 and tyrosine-15.
1995,
Pubmed
,
Xenbase
Murakami,
Analysis of the early embryonic cell cycles of Xenopus; regulation of cell cycle length by Xe-wee1 and Mos.
1998,
Pubmed
,
Xenbase
Murray,
Cell cycle extracts.
1991,
Pubmed
Muslin,
Interaction of 14-3-3 with signaling proteins is mediated by the recognition of phosphoserine.
1996,
Pubmed
,
Xenbase
O'Connell,
The G2-phase DNA-damage checkpoint.
2000,
Pubmed
O'Connell,
Chk1 is a wee1 kinase in the G2 DNA damage checkpoint inhibiting cdc2 by Y15 phosphorylation.
1997,
Pubmed
Ohi,
Regulating the onset of mitosis.
1999,
Pubmed
,
Xenbase
Parker,
Cyclin promotes the tyrosine phosphorylation of p34cdc2 in a wee1+ dependent manner.
1991,
Pubmed
Parker,
Inactivation of the p34cdc2-cyclin B complex by the human WEE1 tyrosine kinase.
1992,
Pubmed
Peng,
Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216.
1997,
Pubmed
Price,
Drosophila wee1 has an essential role in the nuclear divisions of early embryogenesis.
2000,
Pubmed
Raleigh,
The G(2) DNA damage checkpoint targets both Wee1 and Cdc25.
2000,
Pubmed
Rowley,
The wee1 protein kinase is required for radiation-induced mitotic delay.
1992,
Pubmed
Sanchez,
Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25.
1997,
Pubmed
Thorson,
14-3-3 proteins are required for maintenance of Raf-1 phosphorylation and kinase activity.
1998,
Pubmed
Wang,
Binding of 14-3-3beta to the carboxyl terminus of Wee1 increases Wee1 stability, kinase activity, and G2-M cell population.
2000,
Pubmed
Watanabe,
Regulation of the human WEE1Hu CDK tyrosine 15-kinase during the cell cycle.
1995,
Pubmed
Yaffe,
The structural basis for 14-3-3:phosphopeptide binding specificity.
1997,
Pubmed
Yang,
Maintenance of G2 arrest in the Xenopus oocyte: a role for 14-3-3-mediated inhibition of Cdc25 nuclear import.
1999,
Pubmed
,
Xenbase
Zeng,
Replication checkpoint requires phosphorylation of the phosphatase Cdc25 by Cds1 or Chk1.
1998,
Pubmed
Zeng,
DNA damage and replication checkpoints in fission yeast require nuclear exclusion of the Cdc25 phosphatase via 14-3-3 binding.
1999,
Pubmed
