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Mol Biol Cell
2005 Dec 01;1612:5749-60. doi: 10.1091/mbc.e05-06-0541.
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Changes in regulatory phosphorylation of Cdc25C Ser287 and Wee1 Ser549 during normal cell cycle progression and checkpoint arrests.
Stanford JS
,
Ruderman JV
.
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Entry into mitosis is catalyzed by cdc2 kinase. Previous work identified the cdc2-activating phosphatase cdc25C and the cdc2-inhibitory kinase wee1 as targets of the incomplete replication-induced kinase Chk1. Further work led to the model that checkpoint kinases block mitotic entry by inhibiting cdc25C through phosphorylation on Ser287 and activating wee1 through phosphorylation on Ser549. However, almost all conclusions underlying this idea were drawn from work using recombinant proteins. Here, we report that in the early Xenopus egg cell cycles, phosphorylation of endogenous cdc25C Ser287 is normally high during interphase and shows no obvious increase after checkpoint activation. By contrast, endogenous wee1 Ser549 phosphorylation is low during interphase and increases after activation of either the DNA damage or replication checkpoints; this is accompanied by a slight increase in wee1 kinase activity. Blocking mitotic entry by adding the catalytic subunit of PKA also results in increased wee1 Ser549 phosphorylation and maintenance of cdc25C Ser287 phosphorylation. These results argue that in response to checkpoint activation, endogenous wee1 is indeed a critical responder that functions by repressing the cdc2-cdc25C positive feedback loop. Surprisingly, endogenous wee1 Ser549 phosphorylation is highest during mitosis just after the peak of cdc2 activity. Treatments that block inactivation of cdc2 result in further increases in wee1 Ser549 phosphorylation, suggesting a previously unsuspected role for wee1 in mitosis.
Anderson,
Processing of adenovirus 2-induced proteins.
1973, Pubmed
Anderson,
Processing of adenovirus 2-induced proteins.
1973,
Pubmed
Atherton-Fessler,
Mechanisms of p34cdc2 regulation.
1993,
Pubmed
Ayad,
Tome-1, a trigger of mitotic entry, is degraded during G1 via the APC.
2003,
Pubmed
,
Xenbase
Baldin,
Subcellular localisation of human wee1 kinase is regulated during the cell cycle.
1995,
Pubmed
Berry,
Regulation of Cdc2 activity by phosphorylation at T14/Y15.
1996,
Pubmed
Bitangcol,
Activation of the p42 mitogen-activated protein kinase pathway inhibits Cdc2 activation and entry into M-phase in cycling Xenopus egg extracts.
1998,
Pubmed
,
Xenbase
Bulavin,
Phosphorylation of Xenopus Cdc25C at Ser285 interferes with ability to activate a DNA damage replication checkpoint in pre-midblastula embryos.
2003,
Pubmed
,
Xenbase
Bulavin,
Dual phosphorylation controls Cdc25 phosphatases and mitotic entry.
2003,
Pubmed
,
Xenbase
Chau,
Mos-induced p42 mitogen-activated protein kinase activation stabilizes M-phase in Xenopus egg extracts after cyclin destruction.
1998,
Pubmed
,
Xenbase
Chau,
Inactivation of p42 mitogen-activated protein kinase is required for exit from M-phase after cyclin destruction.
1999,
Pubmed
,
Xenbase
Chun,
Phosphorylation of Cdc25C by pp90Rsk contributes to a G2 cell cycle arrest in Xenopus cycling egg extracts.
2005,
Pubmed
,
Xenbase
Crane,
Requirements for the destruction of human Aurora-A.
2004,
Pubmed
,
Xenbase
Dalal,
Cytoplasmic localization of human cdc25C during interphase requires an intact 14-3-3 binding site.
1999,
Pubmed
Devault,
Cyclin A potentiates maturation-promoting factor activation in the early Xenopus embryo via inhibition of the tyrosine kinase that phosphorylates cdc2.
1992,
Pubmed
,
Xenbase
Duckworth,
G2 arrest in Xenopus oocytes depends on phosphorylation of cdc25 by protein kinase A.
2002,
Pubmed
,
Xenbase
Fernandez,
Implications for cAMP-dependent protein kinase in the maintenance of the interphase state.
1995,
Pubmed
Finidori-Lepicard,
Progesterone inhibits membrane-bound adenylate cyclase in Xenopus laevis oocytes.
1981,
Pubmed
,
Xenbase
Gabrielli,
Cytoplasmic accumulation of cdc25B phosphatase in mitosis triggers centrosomal microtubule nucleation in HeLa cells.
1996,
Pubmed
Gautier,
Cyclin B in Xenopus oocytes: implications for the mechanism of pre-MPF activation.
1991,
Pubmed
,
Xenbase
Graves,
Localization of human Cdc25C is regulated both by nuclear export and 14-3-3 protein binding.
2001,
Pubmed
Grieco,
A role for cAMP-dependent protein kinase in early embryonic divisions.
1994,
Pubmed
,
Xenbase
Grieco,
Requirement for cAMP-PKA pathway activation by M phase-promoting factor in the transition from mitosis to interphase.
1996,
Pubmed
,
Xenbase
Guo,
Response of Xenopus Cds1 in cell-free extracts to DNA templates with double-stranded ends.
2000,
Pubmed
,
Xenbase
Hoffmann,
Phosphorylation and activation of human cdc25-C by cdc2--cyclin B and its involvement in the self-amplification of MPF at mitosis.
1993,
Pubmed
,
Xenbase
Holloway,
Anaphase is initiated by proteolysis rather than by the inactivation of maturation-promoting factor.
1993,
Pubmed
,
Xenbase
Honda,
Mouse p87wee1 kinase is regulated by M-phase specific phosphorylation.
1995,
Pubmed
Honda,
14-3-3 zeta protein binds to the carboxyl half of mouse wee1 kinase.
1997,
Pubmed
Huchon,
The pure inhibitor of cAMP-dependent protein kinase initiates Xenopus laevis meiotic maturation. A 4-step scheme for meiotic maturation.
1981,
Pubmed
,
Xenbase
Hutchins,
Dephosphorylation of the inhibitory phosphorylation site S287 in Xenopus Cdc25C by protein phosphatase-2A is inhibited by 14-3-3 binding.
2002,
Pubmed
,
Xenbase
Hutchins,
Regulation of Cdc2/cyclin B activation in Xenopus egg extracts via inhibitory phosphorylation of Cdc25C phosphatase by Ca(2+)/calmodulin-dependent protein [corrected] kinase II.
2003,
Pubmed
,
Xenbase
Izumi,
Periodic changes in phosphorylation of the Xenopus cdc25 phosphatase regulate its activity.
1992,
Pubmed
,
Xenbase
Izumi,
Elimination of cdc2 phosphorylation sites in the cdc25 phosphatase blocks initiation of M-phase.
1993,
Pubmed
,
Xenbase
Izumi,
Phosphorylation and activation of the Xenopus Cdc25 phosphatase in the absence of Cdc2 and Cdk2 kinase activity.
1995,
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,
Regulation of the cdc25 protein during the cell cycle in Xenopus extracts.
1992,
Pubmed
,
Xenbase
Kumagai,
14-3-3 proteins act as negative regulators of the mitotic inducer Cdc25 in Xenopus egg extracts.
1998,
Pubmed
,
Xenbase
Lahav-Baratz,
Reversible phosphorylation controls the activity of cyclosome-associated cyclin-ubiquitin ligase.
1995,
Pubmed
Lammer,
The cdc25B phosphatase is essential for the G2/M phase transition in human cells.
1998,
Pubmed
Lee,
Positive regulation of Wee1 by Chk1 and 14-3-3 proteins.
2001,
Pubmed
,
Xenbase
Lee,
mik1+ encodes a tyrosine kinase that phosphorylates p34cdc2 on tyrosine 15.
1994,
Pubmed
Lew,
Regulatory roles of cyclin dependent kinase phosphorylation in cell cycle control.
1996,
Pubmed
Liu,
The human Myt1 kinase preferentially phosphorylates Cdc2 on threonine 14 and localizes to the endoplasmic reticulum and Golgi complex.
1997,
Pubmed
,
Xenbase
Lopez-Girona,
Nuclear localization of Cdc25 is regulated by DNA damage and a 14-3-3 protein.
1999,
Pubmed
Luca,
Both cyclin A delta 60 and B delta 97 are stable and arrest cells in M-phase, but only cyclin B delta 97 turns on cyclin destruction.
1991,
Pubmed
,
Xenbase
Lupardus,
A requirement for replication in activation of the ATR-dependent DNA damage checkpoint.
2002,
Pubmed
,
Xenbase
Maller,
Early effect of progesterone on levels of cyclic adenosine 3':5'-monophosphate in Xenopus oocytes.
1979,
Pubmed
,
Xenbase
Maller,
Progesterone-stimulated meiotic cell division in Xenopus oocytes. Induction by regulatory subunit and inhibition by catalytic subunit of adenosine 3':5'-monophosphate-dependent protein kinase.
1977,
Pubmed
,
Xenbase
Manke,
MAPKAP kinase-2 is a cell cycle checkpoint kinase that regulates the G2/M transition and S phase progression in response to UV irradiation.
2005,
Pubmed
Margolis,
PP1 control of M phase entry exerted through 14-3-3-regulated Cdc25 dephosphorylation.
2003,
Pubmed
,
Xenbase
Margolis,
When the checkpoints have gone: insights into Cdc25 functional activation.
2004,
Pubmed
,
Xenbase
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
Mueller,
Cell cycle regulation of a Xenopus Wee1-like kinase.
1995,
Pubmed
,
Xenbase
Mueller,
Measurement of Wee kinase activity.
2005,
Pubmed
,
Xenbase
Mulner,
Cyclic AMP synthesis in Xenopus laevis oocytes: inhibition by progesterone.
1979,
Pubmed
,
Xenbase
Murray,
The role of cyclin synthesis and degradation in the control of maturation promoting factor activity.
1989,
Pubmed
,
Xenbase
Murray,
Cell cycle extracts.
1991,
Pubmed
Murray,
Real time observation of anaphase in vitro.
1996,
Pubmed
,
Xenbase
Nishijima,
A dual-specificity phosphatase Cdc25B is an unstable protein and triggers p34(cdc2)/cyclin B activation in hamster BHK21 cells arrested with hydroxyurea.
1997,
Pubmed
O'Connor,
Inhibition of oocyte maturation by theophylline: possible mechanism of action.
1976,
Pubmed
,
Xenbase
Ogg,
Purification of a serine kinase that associates with and phosphorylates human Cdc25C on serine 216.
1994,
Pubmed
Ouyang,
The physical association and phosphorylation of Cdc25C protein phosphatase by Prk.
1999,
Pubmed
Parker,
Identification of a 95-kDa WEE1-like tyrosine kinase in HeLa cells.
1995,
Pubmed
Peng,
Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216.
1997,
Pubmed
Peng,
C-TAK1 protein kinase phosphorylates human Cdc25C on serine 216 and promotes 14-3-3 protein binding.
1998,
Pubmed
Perdiguero,
Regulation of Cdc25C activity during the meiotic G2/M transition.
2004,
Pubmed
,
Xenbase
Rothblum-Oviatt,
14-3-3 binding regulates catalytic activity of human Wee1 kinase.
2001,
Pubmed
Sadler,
Progesterone inhibits adenylate cyclase in Xenopus oocytes. Action on the guanine nucleotide regulatory protein.
1981,
Pubmed
,
Xenbase
Sancar,
Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints.
2004,
Pubmed
Sanchez,
Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25.
1997,
Pubmed
Schmitt,
Inhibition of Xenopus oocyte meiotic maturation by catalytically inactive protein kinase A.
2002,
Pubmed
,
Xenbase
Sia,
Control of Swe1p degradation by the morphogenesis checkpoint.
1998,
Pubmed
Smith,
Wee1-regulated apoptosis mediated by the crk adaptor protein in Xenopus egg extracts.
2000,
Pubmed
,
Xenbase
Smythe,
Coupling of mitosis to the completion of S phase in Xenopus occurs via modulation of the tyrosine kinase that phosphorylates p34cdc2.
1992,
Pubmed
,
Xenbase
Solomon,
Cyclin activation of p34cdc2.
1990,
Pubmed
,
Xenbase
Speaker,
Cyclic nucleotide fluctuations during steroid induced meiotic maturation of frog oocytes.
1977,
Pubmed
Strausfeld,
Activation of p34cdc2 protein kinase by microinjection of human cdc25C into mammalian cells. Requirement for prior phosphorylation of cdc25C by p34cdc2 on sites phosphorylated at mitosis.
1994,
Pubmed
Tang,
Two distinct mechanisms for negative regulation of the Wee1 protein kinase.
1993,
Pubmed
,
Xenbase
Verma,
Ubistatins inhibit proteasome-dependent degradation by binding the ubiquitin chain.
2004,
Pubmed
,
Xenbase
Walter,
Induction of a G2-phase arrest in Xenopus egg extracts by activation of p42 mitogen-activated protein kinase.
1997,
Pubmed
,
Xenbase
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
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
Zhou,
Caffeine abolishes the mammalian G(2)/M DNA damage checkpoint by inhibiting ataxia-telangiectasia-mutated kinase activity.
2000,
Pubmed
