Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
We have examined the roles of type-1 (PP-1) and type-2A (PP-2A) protein-serine/threonine phosphatases in the mechanism of activation of p34cdc2/cyclin B protein kinase in Xenopus egg extracts. p34cdc2/cyclin B is prematurely activated in the extracts by inhibition of PP-2A by okadaic acid but not by specific inhibition of PP-1 by inhibitor-2. Activation of the kinase can be blocked by addition of the purified catalytic subunit of PP-2A at a twofold excess over the activity in the extract. The catalytic subunit of PP-1 can also block kinase activation, but very high levels of activity are required. Activation of p34cdc2/cyclin B protein kinase requires dephosphorylation of p34cdc2 on Tyr15. This reaction is catalysed by cdc25-C phosphatase that is itself activated by phosphorylation. We show that, in interphase extracts, inhibition of PP-2A by okadaic acid completely blocks cdc25-C dephosphorylation, whereas inhibition of PP-1 by specific inhibitors has no effect. This indicates that a type-2A protein phosphatase negatively regulates p34cdc2/cyclin B protein kinase activation primarily by maintaining cdc25-C phosphatase in a dephosphorylated, low activity state. In extracts containing active p34cdc2/cyclin B protein kinase, dephosphorylation of cdc25-C is inhibited, whereas the activity of PP-2A (and PP-1) towards other substrates is unaffected. We propose that this specific inhibition of cdc25-C dephosphorylation is part of a positive feedback loop that also involves direct phosphorylation and activation of cdc25-C by p34cdc2/cyclin B. Dephosphorylation of cdc25-C is also inhibited when cyclin A-dependent protein kinase is active, and this may explain the potentiation of p34cdc2/cyclin B protein kinase activation by cyclin A. In extracts supplemented with nuclei, the block on p34cdc2/cyclin B activation by unreplicated DNA is abolished when PP-2A is inhibited or when stably phosphorylated cdc25-C is added, but not when PP-1 is specifically inhibited. This suggests that unreplicated DNA inhibits p34cdc2/cyclin B activation by maintaining cdc25-C in a low activity, dephosphorylated state, probably by keeping the activity of a type-2A protein phosphatase towards cdc25-C at a high level.
Agostinis,
Specificity of the polycation-stimulated (type-2A) and ATP,Mg-dependent (type-1) protein phosphatases toward substrates phosphorylated by P34cdc2 kinase.
1992, Pubmed
Agostinis,
Specificity of the polycation-stimulated (type-2A) and ATP,Mg-dependent (type-1) protein phosphatases toward substrates phosphorylated by P34cdc2 kinase.
1992,
Pubmed
Axton,
One of the protein phosphatase 1 isoenzymes in Drosophila is essential for mitosis.
1990,
Pubmed
Booher,
Involvement of a type 1 protein phosphatase encoded by bws1+ in fission yeast mitotic control.
1989,
Pubmed
Buendia,
Regulation of protein kinases associated with cyclin A and cyclin B and their effect on microtubule dynamics and nucleation in Xenopus egg extracts.
1991,
Pubmed
,
Xenbase
Clarke,
Cyclin A- and cyclin B-dependent protein kinases are regulated by different mechanisms in Xenopus egg extracts.
1992,
Pubmed
,
Xenbase
Clarke,
Regulation of p34cdc2 protein kinase: new insights into protein phosphorylation and the cell cycle.
1991,
Pubmed
Cohen,
An improved procedure for identifying and quantitating protein phosphatases in mammalian tissues.
1989,
Pubmed
Cohen,
The structure and regulation of protein phosphatases.
1989,
Pubmed
Cohen,
Protein phosphatase-1 and protein phosphatase-2A from rabbit skeletal muscle.
1988,
Pubmed
Cohen,
Cloning of protein-serine/threonine phosphatases.
1991,
Pubmed
Cohen,
Classification of protein-serine/threonine phosphatases: identification and quantitation in cell extracts.
1991,
Pubmed
Dasso,
Completion of DNA replication is monitored by a feedback system that controls the initiation of mitosis in vitro: studies in Xenopus.
1990,
Pubmed
,
Xenbase
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
Doonan,
The bimG gene of Aspergillus nidulans, required for completion of anaphase, encodes a homolog of mammalian phosphoprotein phosphatase 1.
1989,
Pubmed
Ducommun,
cdc2 phosphorylation is required for its interaction with cyclin.
1991,
Pubmed
,
Xenbase
Dunphy,
The cdc25 protein contains an intrinsic phosphatase activity.
1991,
Pubmed
Eckstein,
Nucleoside phosphorothioates.
1985,
Pubmed
Enoch,
Coupling M phase and S phase: controls maintaining the dependence of mitosis on chromosome replication.
1991,
Pubmed
Felix,
A post-ribosomal supernatant from activated Xenopus eggs that displays post-translationally regulated oscillation of its cdc2+ mitotic kinase activity.
1989,
Pubmed
,
Xenbase
Félix,
Cdc2 H1 kinase is negatively regulated by a type 2A phosphatase in the Xenopus early embryonic cell cycle: evidence from the effects of okadaic acid.
1990,
Pubmed
,
Xenbase
Foulkes,
In vivo actions of protein phosphatase inhibitor-2 in Xenopus oocytes.
1982,
Pubmed
,
Xenbase
Galaktionov,
Specific activation of cdc25 tyrosine phosphatases by B-type cyclins: evidence for multiple roles of mitotic cyclins.
1991,
Pubmed
Gautier,
cdc25 is a specific tyrosine phosphatase that directly activates p34cdc2.
1991,
Pubmed
,
Xenbase
Glotzer,
Cyclin is degraded by the ubiquitin pathway.
1991,
Pubmed
,
Xenbase
Goris,
Okadaic acid, a specific protein phosphatase inhibitor, induces maturation and MPF formation in Xenopus laevis oocytes.
1989,
Pubmed
,
Xenbase
Gould,
Tyrosine phosphorylation of the fission yeast cdc2+ protein kinase regulates entry into mitosis.
1989,
Pubmed
Gould,
Phosphorylation at Thr167 is required for Schizosaccharomyces pombe p34cdc2 function.
1991,
Pubmed
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
Honda,
The cell cycle regulator, human p50weel, is a tyrosine kinase and not a serine/tyrosine kinase.
1992,
Pubmed
Huchon,
Protein phosphatase-1 is involved in Xenopus oocyte maturation.
1981,
Pubmed
,
Xenbase
Hunt,
Cyclins and their partners: from a simple idea to complicated reality.
1991,
Pubmed
Igarashi,
Wee1(+)-like gene in human cells.
1991,
Pubmed
Izumi,
Periodic changes in phosphorylation of the Xenopus cdc25 phosphatase regulate its activity.
1992,
Pubmed
,
Xenbase
Jessus,
Oscillation of MPF is accompanied by periodic association between cdc25 and cdc2-cyclin B.
1992,
Pubmed
,
Xenbase
Karsenti,
Interconversion of metaphase and interphase microtubule arrays, as studied by the injection of centrosomes and nuclei into Xenopus eggs.
1984,
Pubmed
,
Xenbase
Kinoshita,
Sister-chromatid separation and protein dephosphorylation in mitosis.
1991,
Pubmed
Kinoshita,
Distinct, essential roles of type 1 and 2A protein phosphatases in the control of the fission yeast cell division cycle.
1990,
Pubmed
Krek,
Differential phosphorylation of vertebrate p34cdc2 kinase at the G1/S and G2/M transitions of the cell cycle: identification of major phosphorylation sites.
1991,
Pubmed
Krek,
Mutations of p34cdc2 phosphorylation sites induce premature mitotic events in HeLa cells: evidence for a double block to p34cdc2 kinase activation in vertebrates.
1991,
Pubmed
Krek,
Cell cycle regulation of vertebrate p34cdc2 activity: identification of Thr161 as an essential in vivo phosphorylation site.
1992,
Pubmed
Kumagai,
The cdc25 protein controls tyrosine dephosphorylation of the cdc2 protein in a cell-free system.
1991,
Pubmed
,
Xenbase
Kumagai,
Regulation of the cdc25 protein during the cell cycle in Xenopus extracts.
1992,
Pubmed
,
Xenbase
Langan,
Mammalian growth-associated H1 histone kinase: a homolog of cdc2+/CDC28 protein kinases controlling mitotic entry in yeast and frog cells.
1989,
Pubmed
,
Xenbase
Lee,
cdc25+ encodes a protein phosphatase that dephosphorylates p34cdc2.
1992,
Pubmed
,
Xenbase
Lee,
INH, a negative regulator of MPF, is a form of protein phosphatase 2A.
1991,
Pubmed
,
Xenbase
Lehner,
The roles of Drosophila cyclins A and B in mitotic control.
1990,
Pubmed
Lehner,
Expression and function of Drosophila cyclin A during embryonic cell cycle progression.
1989,
Pubmed
Lorca,
Dephosphorylation of cdc2 on threonine 161 is required for cdc2 kinase inactivation and normal anaphase.
1992,
Pubmed
,
Xenbase
Lundgren,
mik1 and wee1 cooperate in the inhibitory tyrosine phosphorylation of cdc2.
1991,
Pubmed
MacKintosh,
Cyanobacterial microcystin-LR is a potent and specific inhibitor of protein phosphatases 1 and 2A from both mammals and higher plants.
1990,
Pubmed
McGowan,
Human Wee1 kinase inhibits cell division by phosphorylating p34cdc2 exclusively on Tyr15.
1993,
Pubmed
Millar,
p55CDC25 is a nuclear protein required for the initiation of mitosis in human cells.
1991,
Pubmed
Millar,
p80cdc25 mitotic inducer is the tyrosine phosphatase that activates p34cdc2 kinase in fission yeast.
1991,
Pubmed
Millar,
cdc25 M-phase inducer.
1991,
Pubmed
Minshull,
The A- and B-type cyclin associated cdc2 kinases in Xenopus turn on and off at different times in the cell cycle.
1990,
Pubmed
,
Xenbase
Murray,
Creative blocks: cell-cycle checkpoints and feedback controls.
1992,
Pubmed
Murray,
The role of cyclin synthesis and degradation in the control of maturation promoting factor activity.
1989,
Pubmed
,
Xenbase
Murray,
Cyclin synthesis drives the early embryonic cell cycle.
1989,
Pubmed
,
Xenbase
Norbury,
Regulatory phosphorylation of the p34cdc2 protein kinase in vertebrates.
1991,
Pubmed
,
Xenbase
Nurse,
Universal control mechanism regulating onset of M-phase.
1990,
Pubmed
Ohkura,
The fission yeast dis2+ gene required for chromosome disjoining encodes one of two putative type 1 protein phosphatases.
1989,
Pubmed
Pagano,
Cyclin A is required at two points in the human cell cycle.
1992,
Pubmed
Parker,
Inactivation of the p34cdc2-cyclin B complex by the human WEE1 tyrosine kinase.
1992,
Pubmed
Parker,
p107wee1 is a dual-specificity kinase that phosphorylates p34cdc2 on tyrosine 15.
1992,
Pubmed
Philpott,
Sperm decondensation in Xenopus egg cytoplasm is mediated by nucleoplasmin.
1991,
Pubmed
,
Xenbase
Picking,
Fluorescence studies on the interaction of inhibitor 2 and okadaic acid with the catalytic subunit of type 1 phosphoprotein phosphatases.
1991,
Pubmed
Pines,
Molecular cloning and characterization of the mRNA for cyclin from sea urchin eggs.
1987,
Pubmed
,
Xenbase
Pines,
Cyclin-dependent kinases: a new cell cycle motif?
1991,
Pubmed
Russell,
The mitotic inducer nim1+ functions in a regulatory network of protein kinase homologs controlling the initiation of mitosis.
1987,
Pubmed
Russell,
Negative regulation of mitosis by wee1+, a gene encoding a protein kinase homolog.
1987,
Pubmed
Sadhu,
Human homolog of fission yeast cdc25 mitotic inducer is predominantly expressed in G2.
1990,
Pubmed
Smith,
Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase.
1988,
Pubmed
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
Sola,
p34cdc2 phosphorylation sites in histone H1 are dephosphorylated by protein phosphatase 2A1.
1991,
Pubmed
Solomon,
Role of phosphorylation in p34cdc2 activation: identification of an activating kinase.
1992,
Pubmed
,
Xenbase
Solomon,
Cyclin activation of p34cdc2.
1990,
Pubmed
,
Xenbase
Strausfeld,
Dephosphorylation and activation of a p34cdc2/cyclin B complex in vitro by human CDC25 protein.
1991,
Pubmed
Swenson,
The clam embryo protein cyclin A induces entry into M phase and the resumption of meiosis in Xenopus oocytes.
1986,
Pubmed
,
Xenbase
Tung,
The catalytic subunits of protein phosphatase-1 and protein phosphatase 2A are distinct gene products.
1984,
Pubmed
Walker,
Role for cyclin A in the dependence of mitosis on completion of DNA replication.
1991,
Pubmed
,
Xenbase
Walker,
Multiple roles for protein phosphatase 1 in regulating the Xenopus early embryonic cell cycle.
1992,
Pubmed
,
Xenbase
Yanagida,
Protein phosphatases and cell division cycle control.
1992,
Pubmed
