XB-ART-4613
Mol Biol Cell
2003 Oct 01;1410:4003-14. doi: 10.1091/mbc.e03-02-0061.
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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.
Hutchins JR, Dikovskaya D, Clarke PR.
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Activation of Cdc2/cyclin B kinase and entry into mitosis requires dephosphorylation of inhibitory sites on Cdc2 by Cdc25 phosphatase. In vertebrates, Cdc25C is inhibited by phosphorylation at a single site targeted by the checkpoint kinases Chk1 and Cds1/Chk2 in response to DNA damage or replication arrest. In Xenopus early embryos, the inhibitory site on Cdc25C (S287) is also phosphorylated by a distinct protein kinase that may determine the intrinsic timing of the cell cycle. We show that S287-kinase activity is repressed in extracts of unfertilized Xenopus eggs arrested in M phase but is rapidly stimulated upon release into interphase by addition of Ca2+, which mimics fertilization. S287-kinase activity is not dependent on cyclin B degradation or inactivation of Cdc2/cyclin B kinase, indicating a direct mechanism of activation by Ca2+. Indeed, inhibitor studies identify the predominant S287-kinase as Ca2+/calmodulin-dependent protein kinase II (CaMKII). CaMKII phosphorylates Cdc25C efficiently on S287 in vitro and, like Chk1, is inhibited by 7-hydroxystaurosporine (UCN-01) and debromohymenialdisine, compounds that abrogate G2 arrest in somatic cells. CaMKII delays Cdc2/cyclin B activation via phosphorylation of Cdc25C at S287 in egg extracts, indicating that this pathway regulates the timing of mitosis during the early embryonic cell cycle.
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Species referenced: Xenopus laevis
Genes referenced: camk2g ccnb1.2 cdc25c cdk1 chek1 pold1 ucn
References [+] :
Alemany,
Cmk2, a novel serine/threonine kinase in fission yeast.
2002, Pubmed
Alemany, Cmk2, a novel serine/threonine kinase in fission yeast. 2002, Pubmed
Berridge, Calcium--a life and death signal. 1998, Pubmed
Blasina, A human homologue of the checkpoint kinase Cds1 directly inhibits Cdc25 phosphatase. 1999, Pubmed
Busa, An elevated free cytosolic Ca2+ wave follows fertilization in eggs of the frog, Xenopus laevis. 1985, Pubmed , Xenbase
Busby, The radiosensitizing agent 7-hydroxystaurosporine (UCN-01) inhibits the DNA damage checkpoint kinase hChk1. 2000, Pubmed
Chang, Characterization of a calmodulin kinase II inhibitor protein in brain. 1998, Pubmed
Chen, The 1.7 A crystal structure of human cell cycle checkpoint kinase Chk1: implications for Chk1 regulation. 2000, Pubmed
Clarke, Dephosphorylation of cdc25-C by a type-2A protein phosphatase: specific regulation during the cell cycle in Xenopus egg extracts. 1993, Pubmed , Xenbase
Clarke, Cyclin A- and cyclin B-dependent protein kinases are regulated by different mechanisms in Xenopus egg extracts. 1992, Pubmed , Xenbase
Colbran, Regulatory interactions of the calmodulin-binding, inhibitory, and autophosphorylation domains of Ca2+/calmodulin-dependent protein kinase II. 1988, Pubmed
Curman, Inhibition of the G2 DNA damage checkpoint and of protein kinases Chk1 and Chk2 by the marine sponge alkaloid debromohymenialdisine. 2001, Pubmed
Dalal, Cytoplasmic localization of human cdc25C during interphase requires an intact 14-3-3 binding site. 1999, Pubmed
Dale, Similar substrate recognition motifs for mammalian AMP-activated protein kinase, higher plant HMG-CoA reductase kinase-A, yeast SNF1, and mammalian calmodulin-dependent protein kinase I. 1995, 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
Davies, Specificity and mechanism of action of some commonly used protein kinase inhibitors. 2000, Pubmed
Duckworth, G2 arrest in Xenopus oocytes depends on phosphorylation of cdc25 by protein kinase A. 2002, Pubmed , Xenbase
Dunphy, The decision to enter mitosis. 1994, Pubmed
Falck, The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis. 2001, Pubmed
Feijoo, Activation of mammalian Chk1 during DNA replication arrest: a role for Chk1 in the intra-S phase checkpoint monitoring replication origin firing. 2001, Pubmed
Furnari, Cdc25 inhibited in vivo and in vitro by checkpoint kinases Cds1 and Chk1. 1999, Pubmed
Glass, Isolation of phosphorylated peptides and proteins on ion exchange papers. 1978, Pubmed
Glotzer, Cyclin is degraded by the ubiquitin pathway. 1991, Pubmed , Xenbase
Goldberg, Structural basis for the autoinhibition of calcium/calmodulin-dependent protein kinase I. 1996, Pubmed
Grandin, Cycling of intracellular free calcium and intracellular pH in Xenopus embryos: a possible role in the control of the cell cycle. 1991, Pubmed , Xenbase
Graves, The Chk1 protein kinase and the Cdc25C regulatory pathways are targets of the anticancer agent UCN-01. 2000, 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
Hanks, Protein kinase catalytic domain sequence database: identification of conserved features of primary structure and classification of family members. 1991, Pubmed
Hirose, Abrogation of the Chk1-mediated G(2) checkpoint pathway potentiates temozolomide-induced toxicity in a p53-independent manner in human glioblastoma cells. 2001, 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
Holloway, Anaphase is initiated by proteolysis rather than by the inactivation of maturation-promoting factor. 1993, Pubmed , Xenbase
Hudmon, Structure-function of the multifunctional Ca2+/calmodulin-dependent protein kinase II. 2002, Pubmed
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, Substrate specificity determinants of the checkpoint protein kinase Chk1. 2000, Pubmed , Xenbase
Izumi, Phosphorylation and activation of the Xenopus Cdc25 phosphatase in the absence of Cdc2 and Cdk2 kinase activity. 1995, Pubmed , Xenbase
Izumi, Elimination of cdc2 phosphorylation sites in the cdc25 phosphatase blocks initiation of M-phase. 1993, Pubmed , Xenbase
Izumi, Periodic changes in phosphorylation of the Xenopus cdc25 phosphatase regulate its activity. 1992, Pubmed , Xenbase
Keating, Intracellular free calcium oscillations in normal and cleavage-blocked embryos and artificially activated eggs of Xenopus laevis. 1994, Pubmed , Xenbase
King, A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B. 1995, Pubmed , Xenbase
Kubota, Free calcium wave upon activation in Xenopus eggs. 1987, Pubmed , Xenbase
Kubota, Oscillation of intracellular free calcium in cleaving and cleavage-arrested embryos of Xenopus laevis. 1993, Pubmed , Xenbase
Kumagai, Regulation of the cdc25 protein during the cell cycle in Xenopus extracts. 1992, 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, Purification and molecular cloning of Plx1, a Cdc25-regulatory kinase from Xenopus egg extracts. 1996, 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
Lindsay, Calcium requirements during mitotic cdc2 kinase activation and cyclin degradation in Xenopus egg extracts. 1995, Pubmed , Xenbase
Lohka, Induction of nuclear envelope breakdown, chromosome condensation, and spindle formation in cell-free extracts. 1985, Pubmed , Xenbase
Lopez-Girona, Nuclear localization of Cdc25 is regulated by DNA damage and a 14-3-3 protein. 1999, Pubmed
Lorca, Calmodulin-dependent protein kinase II mediates inactivation of MPF and CSF upon fertilization of Xenopus eggs. 1993, Pubmed , Xenbase
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
Mailand, Rapid destruction of human Cdc25A in response to DNA damage. 2000, Pubmed
Manning, Evolution of protein kinase signaling from yeast to man. 2002, Pubmed
Masui, Cytoplasmic control of nuclear behavior during meiotic maturation of frog oocytes. 1971, Pubmed
Matsumoto, Calcium, calmodulin, and CaMKII requirement for initiation of centrosome duplication in Xenopus egg extracts. 2002, Pubmed , Xenbase
Matsuoka, Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. 1998, Pubmed
Michael, Activation of the DNA replication checkpoint through RNA synthesis by primase. 2000, Pubmed , Xenbase
Minshull, Translation of cyclin mRNA is necessary for extracts of activated xenopus eggs to enter mitosis. 1989, Pubmed , Xenbase
Morin, The proteolysis-dependent metaphase to anaphase transition: calcium/calmodulin-dependent protein kinase II mediates onset of anaphase in extracts prepared from unfertilized Xenopus eggs. 1994, Pubmed , Xenbase
Mueller, Myt1: a membrane-associated inhibitory kinase that phosphorylates Cdc2 on both threonine-14 and tyrosine-15. 1995, Pubmed , Xenbase
Mueller, Cell cycle regulation of a Xenopus Wee1-like kinase. 1995, Pubmed , Xenbase
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
Murray, Creative blocks: cell-cycle checkpoints and feedback controls. 1992, Pubmed
Nicolás, Xenopus Ran-binding protein 1: molecular interactions and effects on nuclear assembly in Xenopus egg extracts. 1997, Pubmed , Xenbase
O'Neill, Determination of substrate motifs for human Chk1 and hCds1/Chk2 by the oriented peptide library approach. 2002, Pubmed
Patel, Calcium/calmodulin-dependent phosphorylation and activation of human Cdc25-C at the G2/M phase transition in HeLa cells. 1999, Pubmed
Payne, Calcium/calmodulin-dependent protein kinase II. Characterization of distinct calmodulin binding and inhibitory domains. 1988, Pubmed
Peng, Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216. 1997, Pubmed
Peter, The APC is dispensable for first meiotic anaphase in Xenopus oocytes. 2001, Pubmed , Xenbase
Planas-Silva, Expression of a constitutive form of calcium/calmodulin dependent protein kinase II leads to arrest of the cell cycle in G2. 1992, Pubmed
Rasmussen, Inhibition of G2/M progression in Schizosaccharomyces pombe by a mutant calmodulin kinase II with constitutive activity. 1994, Pubmed
Reimann, Emi1 is required for cytostatic factor arrest in vertebrate eggs. 2002, Pubmed , Xenbase
Sanchez, Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25. 1997, Pubmed
Sánchez-Piris, The serine/threonine kinase Cmk2 is required for oxidative stress response in fission yeast. 2002, Pubmed
Schulman, Ca2+-dependent protein phosphorylation system in membranes from various tissues, and its activation by "calcium-dependent regulator". 1978, Pubmed
Solomon, Cyclin activation of p34cdc2. 1990, Pubmed , Xenbase
Songyang, A structural basis for substrate specificities of protein Ser/Thr kinases: primary sequence preference of casein kinases I and II, NIMA, phosphorylase kinase, calmodulin-dependent kinase II, CDK5, and Erk1. 1996, Pubmed
Stevens, Cloning and differential expression of new calcium, calmodulin-dependent protein kinase II isoforms in Xenopus laevis oocytes and several adult tissues. 2001, Pubmed , Xenbase
Sudakin, The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis. 1995, Pubmed
Tokmakov, Calcium oscillations in Xenopus egg cycling extracts. , Pubmed , Xenbase
Walworth, rad-dependent response of the chk1-encoded protein kinase at the DNA damage checkpoint. 1996, Pubmed
Walworth, Cell-cycle checkpoint kinases: checking in on the cell cycle. 2000, Pubmed
Wang, UCN-01: a potent abrogator of G2 checkpoint function in cancer cells with disrupted p53. 1996, Pubmed
White, Definition of optimal substrate recognition motifs of Ca2+-calmodulin-dependent protein kinases IV and II reveals shared and distinctive features. 1998, Pubmed