Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.22 (cdc2)
 8,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcium/calmodulin dependent protein kinase II (CaMKII) is a multifunctional serine/threonine protein kinase. We have created a calcium/calmodulin independent form of this enzyme by truncation. Expression of this enzyme fragment in a rabbit reticulocyte lysate yields a constitutive enzyme with specific activity similar to the activated native enzyme. We have established mammalian cell lines that transiently express this constitutive enzyme using the glucocorticoid-inducible mouse mammary tumor virus long terminal repeat. The transient increase in kinase activity results in a complete cessation of cell cycle progression. This block develops as a consequence of a specific arrest of the cell cycle in G2. During the block, increases in histone H1 kinase activity present in p13 beads or anti-cdc2 immunoprecipitates are seen in parallel with the accumulation of cells at G2, arguing that the arrest is not due to a failure to activate cdc2 as a histone H1 kinase. These results suggest that other changes in serine/threonine protein phosphorylation besides those involved in activation of cdc2 as a histone H1 kinase may be necessary for proper G2-M transition.
 ...
PMID:Expression of a constitutive form of calcium/calmodulin dependent protein kinase II leads to arrest of the cell cycle in G2. 137 61

Nonmuscle caldesmon from bovine brain bound to microtubules with a stoichiometry of five tubulin dimers to one molecule of caldesmon with values of Ka 4.5 x 10(5) M-1. The binding of caldesmon to microtubules was inhibited in the presence of Ca2+ and calmodulin. The phosphorylation of caldesmon by cdc2 kinase also eliminated the microtubule-binding activity. These results suggest that caldesmon may play a physiological role in the functions of microtubules.
 ...
PMID:The binding of nonmuscle caldesmon from brain to microtubules. Regulations by Ca(2+)-calmodulin and cdc2 kinase. 154 74

The cell division cycle in eukaryotes contains up to three major transition points; the conversion of quiescent cells to a stage of active proliferation, the initiation of DNA synthesis (S phase) and the induction of mitosis in cells with newly replicated genome (M phase). Within the past years two strategies, have converged to identify, genetically and biochemically a key protein kinase p34 cdc2 that governs the entry into mitosis. In the fission yeast Schizosaccharomyces pombe a number of mutants in the mitotic regulatory circuit have been isolated. A central gene in the network is cdc2 which is essential for the proper execution of mitosis. The cdc2 gene interacts with a number of other genes for correct mitotic control. The Amphibian oocyte, the oocyte from Xenopus laevis particularly, is arrested at the G2 phase of the first meiotic division; when it enters M phase, it contains a dominant regulatory factor known as MPF (M-phase or maturation promoting factor). Purified MPF is an heterodimer formed of two polypeptides p34cdc2 an homologue of the product of the gene cdc2 and p45cdc13 or cyclin an homologue of the product of the gene cdc13. Biochemical studies have revealed that p34cdc2 is a phosphotyrosine protein during the G2 phase of the cell cycle, both mitotic and meiotic. The tyrosine phosphorylation of p34cdc2 is regulated by the gradual accumulation of cyclin. At the onset of M phase, the complex p34cdc2/cyclin is activated as an histone H1 kinase, and p34cdc2 is tyrosine dephosphorylated. The mechanism of activation of p34cdc2 is negatively regulated by a form of protein phosphatase 2A. Ovulated vertebrate oocytes are arrested at metaphase of the second meiotic division (M II) under the control of the proto-oncogene c-mos a protein kinase. The exit of M II phase and the initiation of early embryonic mitotic cell cycles are physiologically induced by the spermatozoa at the time of fertilization. They requires the degradation of c-mos by a Ca2+ dependent proteolytic enzyme and the destruction of cyclin by an ubiquitin dependent pathway. The Xenopus oocyte has led to the molecular elucidation of MPF and identified links between cell cycle control, protein phosphorylation and proto-oncogenes. Despite the impresive progess of recent years, there is still much to be learned about the control of meiosis in Xenopus oocytes.
 ...
PMID:[From ovocyte to biochemistry of the cell cycle]. 165 57

A recent report that mitosis-specific phosphorylation causes the nonmuscle caldesmon to dissociate from microfilaments (Yamashiro, S., Yamakita, Y., Ishikawa, R., and Matsumura, F. (1990) Nature 344, 675-678) suggests that this process may contribute to the major structural reorganization of the eukaryotic cell at mitosis. In this study we have demonstrated that smooth muscle caldesmon is phosphorylated in vitro by cdc2 kinase from mitotic phase HeLa cells to 1.2 mol of phosphate/mol of caldesmon. Tryptic maps showed three major phosphorylated spots and approximately equal amounts of phosphorylated Ser and Thr were identified. F-actin or calmodulin in the presence of Ca2+ blocks the phosphorylation of caldesmon. Phosphorylation of caldesmon greatly reduced its binding to F-actin. The phosphorylation sites were located in a 10,000-Da CnBr fragment at the COOH-terminal end of the caldesmon molecule known to house the binding sites for actin and calmodulin (Bartegi A., Fattoum, A., Derancourt, J., and Kassab, R. (1990) J. Biol. Chem. 265, 15231-15238). Our finding supports the model that phosphorylation of caldesmon by cdc2 kinase at mitosis may contribute to the disassembly of the microfilament bundles during prophase.
 ...
PMID:Phosphorylation of caldesmon by cdc2 kinase. 201 82

The product of the yeast cell cycle control gene cdc2, and its homologs in higher eukaryotes (p34cdc2), all contain a perfectly conserved sequence of 16 amino acids that has not been found in any other protein sequence. Microinjection of this peptide triggers a specific increase in the concentration of intracellular free Ca2+ that originates from intracellular stores in both starfish and Xenopus oocytes. Thus, p34cdc2 might interact through its conserved peptide domain with some component of the Ca2(+)-regulatory system.
 ...
PMID:Microinjection of a conserved peptide sequence of p34cdc2 induces a Ca2+ transient in oocytes. 215 16

In Xenopus embryos, the cell cycle is abbreviated to a rapid alternation between interphase and mitosis. The onset of each M phase is induced by the periodic activation of the cdc2 kinase which is triggered by a threshold level of cyclins and apparently involves dephosphorylation of p34cdc2. We have prepared post-ribosomal supernatants from eggs sampled during interphase (interphase extracts) and just before the first mitosis of the early embryonic cell cycle (prophase extracts). In 'interphase extracts', the cdc2 kinase never activates spontaneously upon incubation at room temperature whereas in 'prophase extracts' it does. We show here that in 'interphase extracts', specific inhibition of type 2A phosphatase by okadaic acid induces cdc2 kinase activation. This requires a subthreshold level of cyclin and the presence of a particulate factor in the extract. Inhibition of type 1 phosphatases by inhibitor 1 and inhibitor 2 never results in cdc2 kinase activation. These results demonstrate that during the period of cyclin accumulation, cdc2 kinase activation is inhibited by a type 2A phosphatase. In 'prophase extracts', spontaneous activation of the cdc2 kinase is inhibited by beta-glycerophosphate and NaF, but not by okadaic acid, inhibitor 1 and inhibitor 2 or divalent cation chelation. This demonstrates that when enough cyclin has accumulated, cdc2 kinase activation involves a protein phosphatase which must be distinct from the type 1 and 2A phosphatases, and from the calcium-dependent (type 2B) and magnesium-dependent (type 2C) phosphatases.
 ...
PMID: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. 215 77

Chromatin condensation and nuclear envelope breakdown are characteristic features of apoptotic cell death, but the mechanisms underlying these phenomena have not been identified. Solubilization of nuclear lamin is responsible for both events in mitosis. In this work, we report that glucocorticoids stimulate rapid degradation of lamin B1 that occurs before oligonucleosomal DNA fragmentation in apoptotic thymocytes. Protease inhibitors and the Ca2+ buffering agent BAPTA-AM block lamin degradation and DNA fragmentation, indicating that the processes are regulated by similar or identical mechanisms. Incubation of isolated thymocyte nuclei with Ca2+ stimulates lamin degradation before the detection of oligonucleosomal DNA fragments. However, in contrast to lamin dissolution during mitosis and some other forms of apoptosis, glucocorticoid-induced degradation of lamin B1 in thymocytes is not accompanied by dephosphorylation-mediated activation of cdc2. Our results demonstrate that lamin degradation is an early feature of apoptosis in thymocytes and suggest that chromatin condensation and breakdown of the nuclear envelope may occur as a result of disruption of nuclear lamina architecture.
 ...
PMID:Degradation of lamin B1 precedes oligonucleosomal DNA fragmentation in apoptotic thymocytes and isolated thymocyte nuclei. 753 14

Intracellular signaling by the second messenger Ca2+ through its receptor calmodulin (CaM) regulates cell function via the activation of CaM-dependent enzymes. Previous studies have shown that cell cycle progression at G1/S and G2/M is sensitive to intracellular CaM levels. However, little is known about the CaM-regulated enzymes involved. Protein phosphorylation has been shown to be important for cell-cycle regulation. Because CaM regulates several protein kinases, and at least one protein phosphatase, our studies are focusing on the roles of these enzymes within the cell cycle. As an initial approach to this problem, cDNAs encoding either normal or mutant calcium/calmodulin kinase II (CaMKII) have been expressed in Schizosaccharomyces pombe. The results show that overexpression of a constitutively active mutant CaMKII caused cell-cycle arrest in G2. Arrest was associated with a failure to activate the p34/cdc2 protein kinase. Expression of the mutant CaMKII in strains of S. pombe with altered timing of mitosis revealed that this effect is not mediated either by cdc25+ or wee1+, suggesting that CaMKII may regulate G2/M progression by another mechanism.
 ...
PMID:Inhibition of G2/M progression in Schizosaccharomyces pombe by a mutant calmodulin kinase II with constitutive activity. 781 47

Cell cycle is regulated by the activation of complexes of cyclins and cyclin-dependent protein kinases at specific points. Quiescent cells lack both cyclins and cyclin-dependent kinases but their expression is induced after proliferative activation. Cyclin A/cdk2 complexes are involved in the onset of DNA replication whereas cyclin B/cdc2 trigger mitosis. We report here that Ca2+ and calmodulin regulate the expression of cdk2, cdc2, cyclin B and the proliferating cell nuclear antigen (a co-factor of DNA polymerase-delta) in human T lymphocytes. Likewise, the expression of cdk4, cyclin A and DNA polymerase-alpha is dependent of the synergistic effect of both the Ca2+/calmodulin and the protein kinase C pathways. Thus, calmodulin controls DNA synthesis by regulating the levels of cdk2 and proliferating cell nuclear antigen and mitosis entry by modulating the expression of cyclin B and cdc2.
 ...
PMID:Calmodulin regulates the expression of cdks, cyclins and replicative enzymes during proliferative activation of human T lymphocytes. 790 33

Oncoprotein 18 (Op18) is a cytosolic protein that was initially identified due to its up-regulated expression in acute leukemia and its complex pattern of phosphorylation in response to diverse extracellular signals. We have previously identified in vivo phosphorylation sites and some of the protein kinase systems involved. Two distinct proline-directed kinase families phosphorylate Ser25 and Ser38 of Op18 with overlapping but distinct site preference. These two kinase families, mitogen-activated protein (MAP) kinases and cyclin-dependent cdc2 kinases, are involved in receptor-regulated and cell-cycle-regulated phosphorylation events, respectively. During analysis of Op18 phosphorylation in the Jurkat T-cell line, we also found that Ser16 of Op18 is phosphorylated in response to a Ca2+ signal generated by T-cell receptor stimulation or the Ca2+ ionophore ionomycin. As suggested by a previous study, T-cell-receptor-induced phosphorylation events may be mediated by the Ca2+/CaM-dependent protein kinase type Gr (CaM kinase-Gr). The present study shows that activation of this protein kinase correlates with phosphorylation of Ser16 of Op18, and in vitro experiments reveal efficient and selective phosphorylation of this residue. The CaM kinase-Gr is only expressed in certain lymphoid cell lines, and the present study shows that ionomycin-induced phosphorylation of Op18 Ser16 is restricted to cells expressing this protein kinase. Finally, CaM kinase-Gr-dependent in vitro phosphorylation of a crude cellular extract reveals a striking preference of this protein kinase for Op18 compared to other cellular substrates. In conclusion, the results suggest that Ser16 of Op18 is a major cytosolic target for activated CaM kinase-Gr.
 ...
PMID:Serine 16 of oncoprotein 18 is a major cytosolic target for the Ca2+/calmodulin-dependent kinase-Gr. 792 72


1 2 3 4 5 6 7 8 9 10 Next >>