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Dephosphorylation of cdc2 on threonine 161 is required for cdc2 kinase inactivation and normal anaphase.
Lorca T, Labbé JC, Devault A, Fesquet D, Capony JP, Cavadore JC, Le Bouffant F, Dorée M.
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Exit from metaphase of the cell cycle requires inactivation of MPF, a stoichiometric complex between the cdc2 catalytic and the cyclin B regulatory subunits, as well as that of cyclin A-cdc2 kinase. Inactivation of both complexes depends on proteolytic degradation of the cyclin subunit, yet cyclin proteolysis is not sufficient to inactivate the H1 kinase activity of cdc2. Genetic evidence strongly suggests that type 1 phosphatase plays a key role in the metaphase-anaphase transition of the cell cycle. Here we report that inhibition of both type 1 and type 2A phosphatases by okadaic acid allows cyclin degradation to occur, but prevents cdc2 kinase inactivation. Complete inhibition of type 2A phosphatase alone is not sufficient to prevent cdc2 kinase inactivation following cyclin proteolysis. We show further that residue 161 of cdc2 is phosphorylated in active cyclin A or cyclin B complexes at metaphase, whilst unassociated cdc2 is not phosphorylated. Proteolysis of cyclin releases a free cdc2 subunit, which subsequently undergoes dephosphorylation and then migrates more slowly than its Thr161 phosphorylated counterpart in Laemmli gels. Removal of phosphothreonine 161 requires cyclin proteolysis. However, it does not occur even after cyclin proteolysis, when both type 1 and type 2A phosphatases are inhibited. We conclude that both cyclin degradation and dephosphorylation of Thr161 on cdc2, catalysed at least in part by type 1 phosphatase, are required to inactivate either cyclin B- or cyclin A-cdc2 kinases and thus for cells to exit from M phase.
Aitken,
Isolation and characterisation of active fragments of protein phosphatase inhibitor-1 from rabbit skeletal muscle.
1982, Pubmed
Aitken,
Isolation and characterisation of active fragments of protein phosphatase inhibitor-1 from rabbit skeletal muscle.
1982,
Pubmed Axton,
One of the protein phosphatase 1 isoenzymes in Drosophila is essential for mitosis.
1990,
Pubmed Belmont,
Real-time visualization of cell cycle-dependent changes in microtubule dynamics in cytoplasmic extracts.
1990,
Pubmed
,
Xenbase Booher,
The fission yeast cdc2/cdc13/suc1 protein kinase: regulation of catalytic activity and nuclear localization.
1989,
Pubmed Boyle,
Phosphopeptide mapping and phosphoamino acid analysis by two-dimensional separation on thin-layer cellulose plates.
1991,
Pubmed Clarke,
Cyclin A- and cyclin B-dependent protein kinases are regulated by different mechanisms in Xenopus egg extracts.
1992,
Pubmed
,
Xenbase Cooper,
Detection and quantification of phosphotyrosine in proteins.
1983,
Pubmed Doonan,
The bimG gene of Aspergillus nidulans, required for completion of anaphase, encodes a homolog of mammalian phosphoprotein phosphatase 1.
1989,
Pubmed Dorée,
Control of M-phase by maturation-promoting factor.
1990,
Pubmed Ducommun,
cdc2 phosphorylation is required for its interaction with cyclin.
1991,
Pubmed
,
Xenbase Fang,
Evidence that the G1-S and G2-M transitions are controlled by different cdc2 proteins in higher eukaryotes.
1991,
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 Félix,
Triggering of cyclin degradation in interphase extracts of amphibian eggs by cdc2 kinase.
1990,
Pubmed
,
Xenbase Ghiara,
A cyclin B homolog in S. cerevisiae: chronic activation of the Cdc28 protein kinase by cyclin prevents exit from mitosis.
1991,
Pubmed Glotzer,
Cyclin is degraded by the ubiquitin pathway.
1991,
Pubmed
,
Xenbase Gould,
Phosphorylation at Thr167 is required for Schizosaccharomyces pombe p34cdc2 function.
1991,
Pubmed Hershko,
Methylated ubiquitin inhibits cyclin degradation in clam embryo extracts.
1991,
Pubmed Hosoya,
Mitosis-specific phosphorylation of myosin light chain kinase.
1991,
Pubmed Hunt,
The requirements for protein synthesis and degradation, and the control of destruction of cyclins A and B in the meiotic and mitotic cell cycles of the clam embryo.
1992,
Pubmed Hutchison,
DNA replication and cell cycle control in Xenopus egg extracts.
1989,
Pubmed
,
Xenbase Inoué,
Cell division and the mitotic spindle.
1981,
Pubmed Karess,
The regulatory light chain of nonmuscle myosin is encoded by spaghetti-squash, a gene required for cytokinesis in Drosophila.
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 Kumagai,
The cdc25 protein controls tyrosine dephosphorylation of the cdc2 protein in a cell-free system.
1991,
Pubmed
,
Xenbase Labbe,
Activation at M-phase of a protein kinase encoded by a starfish homologue of the cell cycle control gene cdc2+.
1988,
Pubmed
,
Xenbase Labbe,
Purification of MPF from starfish: identification as the H1 histone kinase p34cdc2 and a possible mechanism for its periodic activation.
1989,
Pubmed
,
Xenbase Labbé,
M phase-specific cdc2 kinase: preparation from starfish oocytes and properties.
1991,
Pubmed
,
Xenbase Labbé,
MPF from starfish oocytes at first meiotic metaphase is a heterodimer containing one molecule of cdc2 and one molecule of cyclin B.
1989,
Pubmed Laemmli,
Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
1970,
Pubmed Lee,
INH, a negative regulator of MPF, is a form of protein phosphatase 2A.
1991,
Pubmed
,
Xenbase Lischwe,
A new method for partial peptide mapping using N-chlorosuccinimide/urea and peptide silver staining in sodium dodecyl sulfate-polyacrylamide gels.
1982,
Pubmed Lorca,
Degradation of the proto-oncogene product p39mos is not necessary for cyclin proteolysis and exit from meiotic metaphase: requirement for a Ca(2+)-calmodulin dependent event.
1991,
Pubmed
,
Xenbase Lorca,
An okadaic acid-sensitive phosphatase negatively controls the cyclin degradation pathway in amphibian eggs.
1991,
Pubmed
,
Xenbase 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 Mak,
Phosphorylation of caldesmon by cdc2 kinase.
1991,
Pubmed Masui,
Cytoplasmic control of nuclear behavior during meiotic maturation of frog oocytes.
1971,
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 Moreno,
Regulation of p34cdc2 protein kinase during mitosis.
1989,
Pubmed Murray,
Cyclin synthesis drives the early embryonic cell cycle.
1989,
Pubmed
,
Xenbase Murray,
The role of cyclin synthesis and degradation in the control of maturation promoting factor activity.
1989,
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 Otvos,
Solid-phase synthesis of phosphopeptides.
1989,
Pubmed Paris,
Cloning by differential screening of a Xenopus cDNA coding for a protein highly homologous to cdc2.
1991,
Pubmed
,
Xenbase Picard,
Involvement of protein phosphatases 1 and 2A in the control of M phase-promoting factor activity in starfish.
1989,
Pubmed Pines,
Human cyclin A is adenovirus E1A-associated protein p60 and behaves differently from cyclin B.
1990,
Pubmed Pines,
Human cyclins A and B1 are differentially located in the cell and undergo cell cycle-dependent nuclear transport.
1991,
Pubmed Pypaert,
Mitotic cytosol inhibits invagination of coated pits in broken mitotic cells.
1991,
Pubmed Rosenberg,
Vectors for selective expression of cloned DNAs by T7 RNA polymerase.
1987,
Pubmed Roy,
Activation of p34cdc2 kinase by cyclin A.
1991,
Pubmed
,
Xenbase Sagata,
Function of c-mos proto-oncogene product in meiotic maturation in Xenopus oocytes.
1988,
Pubmed
,
Xenbase Schneider,
A one-step purification of membrane proteins using a high efficiency immunomatrix.
1982,
Pubmed Shechter,
Selective chemical cleavage of tryptophanyl peptide bonds by oxidative chlorination with N-chlorosuccinimide.
1976,
Pubmed Solomon,
Role of phosphorylation in p34cdc2 activation: identification of an activating kinase.
1992,
Pubmed
,
Xenbase Tsai,
Isolation of the human cdk2 gene that encodes the cyclin A- and adenovirus E1A-associated p33 kinase.
1991,
Pubmed
,
Xenbase Tuomikoski,
Inhibition of endocytic vesicle fusion in vitro by the cell-cycle control protein kinase cdc2.
,
Pubmed
,
Xenbase Vandré,
Inhibition of mitosis by okadaic acid: possible involvement of a protein phosphatase 2A in the transition from metaphase to anaphase.
1992,
Pubmed Verde,
Regulation of microtubule dynamics by cdc2 protein kinase in cell-free extracts of Xenopus eggs.
1990,
Pubmed
,
Xenbase Wang,
Hepatitis B virus integration in a cyclin A gene in a hepatocellular carcinoma.
1990,
Pubmed Whitfield,
The A- and B-type cyclins of Drosophila are accumulated and destroyed in temporally distinct events that define separable phases of the G2-M transition.
1990,
Pubmed Yamashiro,
Mitosis-specific phosphorylation causes 83K non-muscle caldesmon to dissociate from microfilaments.
1990,
Pubmed
