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Query: EC:2.7.11.22 (cdc2)
 8,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mitotic cell cycle of yeast and animal cells is regulated by the cdc2 gene and its product, the p34 protein kinase, and by other components of the MPF or histone H1 kinase complex. We present evidence that cdc2, p34, and a histone H1 kinase also exist in higher plants. Protein extracts from 10 plant species surveyed display a 34-kDa component recognized by a monoclonal antibody directed against an evolutionarily conserved epitope of fission yeast p34. Nondenatured protein extracts of mitotic Pisum sativum (garden pea) tissues were fractionated by gel filtration, electrophoretically separated under denaturing conditions, and immunoblotted. p34 crossreactive material was apparent in both low and high molecular mass fractions, indicating that pea p34 occurs as both a monomer and as part of a high molecular mass complex. Histone H1 kinase activity was found predominantly in the higher molecular mass fractions, those to which the least phosphorylated form of pea p34 was confined. We also report the cloning of the pea homologue of cdc2 by polymerase chain reaction. DNA sequence analysis reveals perfect conservation of the hallmark "PSTAIR" sequence motif found in all cdc2 gene products analyzed to date.
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PMID:Cell division in higher plants: a cdc2 gene, its 34-kDa product, and histone H1 kinase activity in pea. 216 83

A microassay for p34cdc2 based on the high affinity association between cdc2 and Schizosaccharomyces pombe p13suc1 has been developed. p13 purified from Escherichia coli was immobilized on microtiter plates and cellular lysate was incubated in the wells to allow the binding of cdc2 and its associated proteins. p34cdc2 was assayed either as a histone kinase or by immunological methods. The method was optimized for S. pombe cell extracts but can also be applied to other organisms such as Xenopus oocytes or HeLa cells. This rapid assay allows the specific determination of p34cdc2 histone H1 kinase activity in a very large number of samples.
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PMID:A versatile microtiter assay for the universal cdc2 cell cycle regulator. 216 94

The yeast Cdc7 protein is indispensable to initiation of nuclear DNA replication, based on the phenotype of the conditional, temperature-sensitive (ts) cdc7 mutants at the restrictive temperature. This protein has likewise been implicated in commitment to meiotic DNA recombination and induced mutagenesis, which may result from error-prone DNA repair. Our previous work revealed sequence similarity between the Cdc7 protein and known protein kinases. To determine whether it possesses kinase activity, we have immunoprecipitated the protein from Cdc7-overproducing yeast cells by using polyclonal antibodies raised against a nondenatured beta-galactosidase-Cdc7 fusion protein. In this report, we demonstrate that Cdc7 immune complexes are capable of phosphorylating mammalian histone H1 on serine and/or threonine residues. Immune complexes derived from cells harboring the cdc7-2 ts mutant gene on a high copy number plasmid possess a thermolabile kinase activity. Thus, we postulate that Cdc7 may regulate the various DNA metabolic pathways by phosphorylating one or more target substrates. Because Cdc7 kinase acts downstream of Cdc28/cdc2 kinase function at "start," the transition from G1 to S phase in the cell cycle may be the result of a cascade of protein phosphorylation.
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PMID:DNA metabolism gene CDC7 from yeast encodes a serine (threonine) protein kinase. 216 54

When BHK21 cells synchronized in early S phase were exposed to okadaic acid (OA), an inhibitor of protein phosphatases 1 and 2A, mitosis specific events such as premature chromosome condensation, the production of MPM-2 antigens, dispersion of nuclear lamins and the appearance of mitotic asters were induced, and then disappeared upon further incubation. These mitosis specific events occurred even in the presence of cycloheximide. Within 1 h of exposure to OA, cdc2/histone H1 kinase activity rose 10-fold compared with untreated controls, but returned to the control level upon further incubation. Using antibodies against either p34cdc2 or cyclin B it was found that p34cdc2 complexed with cyclin B was dephosphorylated after OA treatment concomitant with the activation of cdc2 kinase, and that cyclin B was subsequently degraded concomitant with a decrease in cdc2 kinase activity, as in normal mitosis. In contrast, when cells in G1 phase were treated with OA no increase in cdc2 kinase activity was observed. Moreover when cells in pseudo-metaphase induced by nocodazole were treated with OA, cdc2 kinase was inactivated. These results suggest that OA sensitive protein phosphatases control both the activation and inactivation of the p34cdc2 kinase.
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PMID:Okadaic acid, a potent inhibitor of type 1 and type 2A protein phosphatases, activates cdc2/H1 kinase and transiently induces a premature mitosis-like state in BHK21 cells. 217 49

The mammalian homologue of the yeast cdc2 gene product, p34cdc2, is a cell cycle-regulated protein essential for mitosis. We have used polyclonal antisera raised against a peptide corresponding to the carboxyl terminus of the sequence of human cdc2 to study p34cdc2 in Chinese hamster ovary (CHO) cells. Major bands are immunoprecipitated at a molecular weight of 34,000, although not in the presence of competing antigenic peptide. p34cdc2 is coimmunoprecipitated with proteins of molecular weights of 52,000 and 57,000. Immunoprecipitates express histone H1 kinase activity which varies throughout the cell cycle, maximal activity being observed in G2-M. The activity of the p34cdc2 kinase varies according to its association with the Mr 52,000 and 57,000 proteins and according to their phosphorylation state. Treatment of either asynchronous CHO cells or an enriched G2 population with the antitumor agent, etoposide, results in rapid inhibition of immunoprecipitated p34cdc2 kinase activity, which is not due to a direct effect of drug upon the enzyme. p34cdc2 kinase activity recovers as cells arrest in G2 and a second etoposide treatment further inhibits p34cdc2 kinase activity and prolongs G2 arrest. Exposure of asynchronous CHO cells to gamma-irradiation also inhibits p34cdc2 kinase activity within 1 h. Again this activity recovers as cells accumulate in G2. These results suggest that DNA damage in CHO cells elicits a response which results in inhibition of p34cdc2 kinase activity and, consequently, G2 arrest.
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PMID:Inhibition of p34cdc2 kinase activity by etoposide or irradiation as a mechanism of G2 arrest in Chinese hamster ovary cells. 218 1

Genetic studies using fission yeast (Schizosaccharomyces pombe) have identified a gene, cdc2, whose product (p34cdc2) is a protein kinase required for traversal of both the G1 and G2 cell cycle control points. Genetic complementation has been used to demonstrate that p34cdc2 homologues are functionally and structurally conserved in distantly related eukaryotes, and p34cdc2-related proteins are components of both maturation-promoting factor (MPF) and the M phase (growth-associated) histone H1 kinase. The p34cdc2 homologues of multicellular eukaryotes undergo potentially regulatory phosphorylation changes through the cell cycle. Phosphorylation on serine during late G1 is accompanied by a significant increase in p34cdc2 kinase activity which, by analogy with fission yeast, may betray a function related to control over entry into S phase. Phosphorylation on threonine and tyrosine in G2 precedes dephosphorylation of these residues during kinase hyperactivation and entry into mitosis. In addition, long-term control of expression of mammalian p34cdc2 homologues is likely to be exerted at the transcriptional level. These observations provide the framework of a universal model for the control of eukaryotic cell proliferation, in which the p34cdc2 protein kinase integrates multiple cues to signal the initiation of S phase and, subsequently, mitosis.
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PMID:Controls of cell proliferation in yeast and animals. 219 66

Tyrosine phosphorylation of cdc2 is regulated in the cell cycle of mouse 3T3 fibroblasts. Phosphotyrosine in cdc2 is detectable at the onset of DNA synthesis and becomes maximal in the G2 phase of the cell cycle. Quantitative tyrosine dephosphorylation of cdc2 occurs during entry into mitosis and no phosphotyrosine is detected during the G1 phase of the cell cycle. While increasing tyrosine phosphorylation of cdc2 correlates with the formation of a cdc2/p62 complex, the tyrosine phosphorylated cdc2 is inactive as a histone H1 kinase. cdc2 is fully dephosphorylated in its most active mitotic form, yet specific tyrosine dephosphorylation of interphase cdc2 in vitro is insufficient to activate the kinase. In vivo inhibition of tyrosine dephosphorylation by exposure of cells to a phosphatase inhibitor is associated with G2 arrest, which is reversible upon the removal of the phosphatase inhibitor. Tyrosine dephosphorylation of cdc2 may be one of a number of obligatory steps in the mitotic activation of the kinase.
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PMID:Reversible tyrosine phosphorylation of cdc2: dephosphorylation accompanies activation during entry into mitosis. 247 39

In the clam, Spisula, two previously described proteins known as cyclin A and B display the unusual property of selective proteolytic degradation at the end of each mitosis. We show here that clam oocytes and embryos contain a cdc2 protein kinase. This protein kinase is a component of the M phase promoting factor (MPF) in frog eggs and the M phase-specific histone H1 kinase in starfish. Clam cdc2 is found in association with both cyclin A and B, probably not as a trimolecular association, but as separate cdc2/cyclin A and cdc2/cyclin B complexes. Clam cdc2 and the associated cyclins bind to p13suc1-Sepharose. The p13-bound complex, and also anti-cyclin A or B immunoprecipitates, each display cell cycle-dependent histone H1 kinase activity. We suggest that in addition to the cdc2 protein kinase, the cyclins are further components of the M phase promoting factor and that cyclin proteolysis provides the mechanism of MPF inactivation and thus exit from mitosis.
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PMID:Cdc2 protein kinase is complexed with both cyclin A and B: evidence for proteolytic inactivation of MPF. 253 42

The products of the cdc13+ and cdc2+ genes form a stable complex that displays protein kinase activity in vitro. p63cdc13 is a substrate of p34cdc2, the catalytic subunit of the kinase. The histone H1 kinase activity of cdc2 oscillates during the cell cycle. Activation of the preformed cdc2/cdc13 complex at the G2/M transition requires cdc25+ gene function. Post-metaphase inactivation of the kinase is associated with loss of cdc13, which shares sequence homology with mitotic cyclins and, in common with these proteins, is degraded at each cell division. cdc13 and cdc2 co-localize in the cell nucleus. cdc2 is not degraded during mitosis, but in the absence of cdc13 it is not localized in the nucleus. These observations suggest that the cdc13+-encoded cyclin acts to regulate both the catalytic properties and the localization of the protein kinase of which it is a subunit.
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PMID:The fission yeast cdc2/cdc13/suc1 protein kinase: regulation of catalytic activity and nuclear localization. 256 63

p60 is a cellular protein that binds to the adenovirus E1A protein complex in virally infected or transformed human cells. In both infected and uninfected cells, p60 was found in a complex with the cdc2 protein kinase. Immune complexes containing p60 and cdc2 display a cell cycle-dependent histone H1 kinase activity that is most active in interphase. The previously described cdc2-p62/cyclin complex also acts as a histone H1 kinase but is maximally active in mitotic metaphase. The shift in the timing of activation of different cdc2-containing complexes suggests that each might play a distinct role in regulation of the cell cycle.
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PMID:A 60 kd cdc2-associated polypeptide complexes with the E1A proteins in adenovirus-infected cells. 257 Jun 39


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