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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 nin1-1 mutant of Saccharomyces cerevisiae cannot perform the G1/S and G2/M transitions at restrictive temperatures. At such temperatures, nin1-1 strains fail to activate histone H1 kinase after release from alpha factor-imposed G1 block and after release from hydroxyurea-imposed S block. The nin1-1 mutation shows synthetic lethality with certain cdc28 mutant alleles such as cdc28-IN. Two lines of evidence indicate that Nin1p is a component of the 26S proteasome complex: (i) Nin1p, as well as the known component of the 26S proteasome, shifted to the 26S proteasome peak in the glycerol density gradient after preincubation of crude extract with ATP-Mg2+, and (ii) nin1-1 cells accumulated polyubiquitinated proteins under restrictive conditions. These results suggest that activation of Cdc28p kinase requires proteolysis. We have cloned a human cDNA encoding a regulatory subunit of the 26S proteasome, p31, which was found to be a homolog of Nin1p.
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PMID:Nin1p, a regulatory subunit of the 26S proteasome, is necessary for activation of Cdc28p kinase of Saccharomyces cerevisiae. 762 25

Treatment of metaphase II-arrested hamster eggs with activators of protein kinase C has been reported to promote resumption of the cell cycle, second polar body emission, and pronucleus formation (G.I. Gallicano, S.M. Schwarz, R.W. McGaughey, and D.G. Capco, 1993, Dev. Biol. 156, 94-106). In contrast, we have not observed these responses in mouse eggs obtained from CF-1 mice treated with these activators. In this report, we evaluated if this difference was due to differences in the technique used for PKC stimulation in the two different laboratories or due to species differences. Metaphase II-arrested hamster or mouse eggs were treated with phorbol diesters for 5 min or with a membrane-permeable diacylglycerol for 1 hr. Treatment of hamster eggs resulted in (1) the formation of "second polar body-like structures" commencing 5 min after treatment and reaching a maximum by 20-40 min; (2) a remarkable increase in the staining of filamentous actin in the region of these polar body-like structures; and (3) the disassembly of spindle microtubules. A reduction in cdc2/cyclin B1 kinase activity, as assessed by a decrease in H1 kinase activity, as well as progression from metaphase to anaphase were not observed. Treatment of mouse eggs from either CF-1 or CD-1 mice with these activators of PKC did not result in the formation of these polar body-like structures, did not cause an increase in filamentous actin, and did not result in a reduction in histone H1 kinase activity. This treatment, however, did induce disassembly of the spindle microtubules and the formation of multiple "pronucleus-like structures" that were more discernible in eggs from CD-1 mice. We conclude that the "apparent" activation of hamster eggs by activators of PKC is due to the effect of these agents on the cytoskeleton, which gives rise to structures that appear similar to polar bodies, but without any evidence of cell cycle resumption. The different responses seen in mouse and hamster eggs are mainly due to differences in the sensitivity of the cytoskeleton to rearrangements induced by these agents.
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PMID:Differential effect of activators of protein kinase C on cytoskeletal changes in mouse and hamster eggs. 764 80

The retinoblastoma-related protein p130 is a putative negative regulator of cell proliferation in mammalian cells. In this study, p130 is shown to exist in multiple phosphorylated forms in human cells. In glioblastoma T98G cells synchronized by serum deprivation, specific phosphorylated forms of p130 are found at different times after serum re-stimulation. Two phosphorylated forms of p130 only found in serum-arrested T98G cells and in early G1 phase associate with the adenovirus oncoprotein E1A in vitro. One of these two forms corresponds to the in vivo E1A-associated p130 in 293 cells, which express endogenous E1A protein. Moreover, p130 undergoes an abrupt shift to a unique phosphorylated form in mid G1 which is the only p130 form found during the remaining phases of the cell cycle. This phosphorylated form possesses an associated histone H1 kinase activity that is most active in late S phase and G2/M. The cell cycle-dependent expression pattern of cyclins in T98G cells is compatible with cyclin D1/CDK complexes driving the shift to this phosphorylated p130 form in mid G1. These results suggest that the putative growth inhibitory function of p130 is regulated by phosphorylation of this protein. They also suggest that differential phosphorylation of p130 during the cell cycle plays distinct roles in the regulation of p130 function.
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PMID:Cell cycle-dependent phosphorylation of the retinoblastoma-related protein p130. 765 44

Using anti-phosphotyrosine immunoaffinity chromatography, we have searched for serine/threonine kinases that are directly regulated by tyrosine phosphorylation in v-src-transformed rat 3Y1 fibroblasts. Tyrosine phosphoprotein preparations from v-src-transformed cells contain a kinase activity that phosphorylates histone H1 in vitro on serine residues and this activity is present at a 20-fold greater level than that in parental cell preparations. This activity elutes from a MonoQ FPLC column as a single peak and gel filtration chromatography suggests that the kinase has a molecular mass of approximately 55 kDa. Tyrosine phosphatase treatment inactivates the histone H1 kinase and this result indicates that the specific activity of the kinase is regulated by tyrosine phosphorylation. Experiments with cells transformed with a temperature-sensitive mutant of the v-src oncogene demonstrate that the tyrosine phosphorylation of the histone H1 kinase is an early event in v-src transformation. The kinase is distinct from known cdc2 family members that contain the PSTAIR motif, because the kinase can be separated almost completely from these proteins by immunoprecipitation with an antibody against p34cdc2. The profile of antibody reactivity and sensitivity to modulators of protein kinases suggests that this activity is distinct from known second messenger-regulated kinases and from previously characterized MAP kinases.
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PMID:Activation of a histone H1 kinase by tyrosine phosphorylation in v-src-transformed fibroblasts. 767 71

The activities of nuclear histone-H1 kinase and C-kinase as well as the amount of phosphate bound to histone-H1 following partial hepatectomy were studied in rat. It was found that the nuclear histone-H1 kinase activity increased twice within 80 h, first 20 to 30 h, and second at 50 to 70 h after partial hepatectomy. The timing of increase of the enzyme activity correlated with increased amount of bound phosphate. On the other hand, the increase of the C-kinase activities occurred between 5 and 15 h after partial hepatectomy. Antibodies raised against human cdk2, human cyclin-A and mouse cdc2 kinase showed no detectable effect on the nuclear histone H1 kinase activity. These results suggest that phosphorylation of histone-H1 in liver regeneration may be catalysed by a putative kinase(s).
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PMID:Role of nuclear histone-H1 kinase in regeneration of rat liver. 770 10

Recent genetic and functional evidence suggests that the amino terminus of the retinoblastoma (Rb) protein plays an important role in Rb-mediated growth suppression. To explore the mechanism(s) by which this portion of Rb may regulate cell growth, we have sought to characterize cellular proteins that associate with the Rb amino terminus using an in vitro protein-binding assay. Here we report that at least one such protein is a cell cycle-regulated Rb/histone H1 kinase (RbK) whose enzymatic and/or Rb association activity is most prevalent in G2/M phases of cells. In contrast to previously characterized cyclin-dependent and Rb-associated kinases, such as cdk1 (cdc2) and cdk2, G2/M RbK 1) is not depleted by incubation with p13suc-beads, 2) is not detected with antisera against several Rb-associated cyclins-cdks, and 3) associated with Rb via the Rb amino terminus, a region that is dispensable for interaction with other Rb-associated kinases. RbK is clearly distinct from previously characterized mitotic cdks since cyclin A-cdc2, cyclin A-cdk2, cyclin B-cdc2, and cyclin B-cdk2 did not associate with the Rb amino terminus. Coprecipitation experiments with Rb antisera confirmed the association of Rb with a RbK-like kinase in metaphase-arrested cells in vivo. Interestingly, G2/M RbK did not appreciably associate with an analogous portion of p107, a Rb-related protein. Taken together, these data indicate that the Rb amino terminus specifically associates with a novel cell cycle-regulated kinase in late cell cycle stages.
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PMID:Detection of a novel cell cycle-regulated kinase activity that associates with the amino terminus of the retinoblastoma protein in G2/M phases. 772 48

To better understand the relationship between the proliferation of human lymphoid cells and the expression of cdk1, a catalytic subunit of the histone H1 kinase (H1K), we examined its mRNA and protein content in 3 B-cell lines: Ramos, Reh-6 and IARC 963. Cells were elutriated according to their position in the cell cycle. Cell fractions were analyzed for cdk1 mRNA and protein cellular content by Northern blot and immunoblot, respectively, as well as for H1K activity. Both mRNA and protein amounts and H1K activity varied according to cell cycle phase, the lowest values being observed in G1-enriched fractions. For comparison, elutriated fractions were also tested for the expression of cdk2 and cdk4 proteins. Both showed some variations among fractions, but they were less clear than those of cdk1. We also tested 29 samples of lymphoid neoplastic and non-neoplastic tissues for proliferative activity (percentage of S and G2/M cells estimated by flow cytometry) and expression of cdk1, cdk2 and cdk4 proteins. We found a significant correlation between the percentage of cells in S or S + G2/M phases and cdk1 protein content but not cdk2 or cdk4 content. We conclude that cdk1 expression in human lymphoid cells varies during the cell cycle at both mRNA and protein levels.
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PMID:Cdk1 is a marker of proliferation in human lymphoid cells. 772 51

Partial submergence or treatment with either ethylene or gibberellin (GA) promotes rapid internodal growth in deepwater rice (Oryza sativa L.). Earlier work has shown that GA is the immediate hormonal signal for this growth response, which involves induction of the cell cycle at the G2/M phase transition and subsequent enhancement in the rate of DNA synthesis. In all eukaryotes, onset of mitosis is regulated by the p34cdc2/CDC28 protein kinase, whose activity is assayed by in vitro phosphorylation of histone H1. It was found that GA enhanced the activity of p34cdc2/CDC28-like histone H1 kinase in the intercalary meristem of rice internodes. The enzyme activity showed a sharp peak that correlated with a decrease in the population of cells in the G2 phase during the first 4 h of GA treatment but not with changes in DNA synthesis. The level of histone H1 kinase activity increased again when cell division activity in the intercalary meristem is known to be high. The expression of two cdc2 homologs was examined. The mRNA level of one of these, cdc2Os-2, was increased after 1 h of GA treatment, whereas the mRNA level of the other, cdc2Os-1, was not affected. Two cDNAs, cycOs1 and cycOs2, which show high homology to cyclin cDNAs, were cloned from rice. They share 75.1% sequence identity at the amino acid level, and both of them are encoded by mRNAs of 1.6 kb. Expression of the two corresponding cyclin genes was enhanced by GA, and the time course of the induction was compatible with a role for both cyclins in regulating the G2/M phase transition. The cyclins were expressed in the intercalary meristem and the elongation zone of the internode, but the GA-induced increase in transcript levels was restricted to the meristem only. The results support the hypothesis that induction of mitosis by GA is brought about by increased p34cdc2/CDC28 protein kinase activity, which may be the result of transcriptional activation of the cdc2Os-2, cycOs1 and cycOs2 genes.
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PMID:Gibberellin promotes histone H1 kinase activity and the expression of cdc2 and cyclin genes during the induction of rapid growth in deepwater rice internodes. 774 59

Alveolar epithelial cells (AEC) proliferate during embryonic and fetal life, while in the adult lung AEC form a highly differentiated population that does not usually divide. Herein, we tested the hypothesis that differential expression of specific cell cycle control genes may occur during AEC development and transformation. We compared normal rat AEC in primary culture with transformed AEC for the expression of D-type G1 cyclins and cyclin-dependent protein kinases (cdc2 and cdk2). Cyclin D1 mRNA and protein were expressed at comparable levels in both normal rat AEC and in transformed AEC. In contrast, high levels of cyclin D2 mRNA and protein expression were only observed in normal 19-day fetal rat AEC and in transformed mink Mv1Lu cells derived from fetal mink lung epithelium. Moreover, treatment either with antisense oligodeoxynucleotides directed against cyclin D2 mRNA or with genistein (a tyrosine kinase inhibitor) caused significant inhibition of [3H]thymidine incorporation into DNA as well as inhibition of cyclin D2 expression in normal 19-day fetal rat AEC. p34cdc2 (but not p33cdk2 or p34cdk4) was expressed at progressively decreasing levels with corresponding histone H1 kinase activities during rat AEC development (19-day fetal > 21-day fetal > 13-day postnatal > adult rat AEC). The levels of p34cdc2 histone H1 kinase activity were significantly up-regulated or amplified in adult rat type 2 AEC following hyperoxic injury and repair and in transformed AEC. Collectively, these data support an important functional role for cyclin D2 and cdc2 genes in determining the proliferative versus nonproliferative phenotype of AEC during lung development, injury and repair, and transformation.
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PMID:Differential expression of cyclin D2 and cdc2 genes in proliferating and nonproliferating alveolar epithelial cells. 781 75

In Saccharomyces cerevisiae, transient accumulation of G1 cyclin/p34CDC28 (Cdc28p) complexes induces cells to traverse the cell cycle Start checkpoint and commit to a round of cell division. To investigate posttranslational controls that modulate Cdc28p activity during the G1 phase, we have reconstituted cyclin-dependent activation of Cdc28p in a cyclin-depleted G1 extract. A glutathione S-transferase-G1 cyclin chimera (GST-Cln2p) efficiently binds to and activates Cdc28p as a histone H1 kinase. Activation of Cdc28p by GST-Cln2p requires ATP, crude yeast cytosol, and the conserved Thr-169 residue that serves in other organisms as a substrate for phosphorylation by cyclin-dependent protein kinase-activating kinase. This assay may be useful for distinguishing genes that promote directly the posttranslational assembly of active Cln2p/Cdc28p kinase complexes from those that stimulate the accumulation of active complexes via a positive-feedback loop that governs synthesis of G1 cyclins.
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PMID:G1 cyclin-dependent activation of p34CDC28 (Cdc28p) in vitro. 786 57


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