Gene/Protein Disease Symptom Drug Enzyme Compound
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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)

During cell division complete DNA replication must occur before mitosis is initiated. Using a cell-free extract derived from Xenopus eggs that oscillates between S phase and mitosis, we have investigated how completion of DNA synthesis is coupled to the initiation of mitosis. We find that Xenopus eggs contain a feedback pathway which suppresses mitosis until replication is completed and that activation of this inhibitory system is dependent on the presence of a threshold concentration of unreplicated DNA. We demonstrate that in the presence of unreplicated DNA the active feedback system inhibits initiation of mitosis by blocking the activation of MPF, a regulator of mitosis found in all eukaryotic cells. Our results demonstrate that the feedback system does not inhibit MPF activation by blocking the synthesis or accumulation of cyclin protein, a subunit of MPF, or by blocking association of cyclin with the cdc2 subunit of MPF. We propose that the feedback system blocks mitosis by maintaining MPF in an inactive state by modulating posttranslational modifications critical for MPF activation.
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PMID:Completion of DNA replication is monitored by a feedback system that controls the initiation of mitosis in vitro: studies in Xenopus. 216 Aug 59

In Xenopus oocytes, activation of MPF during prophase-metaphase transition is associated with the tyrosine dephosphorylation of the cdc2 protein. In vivo and in cell-free extracts kinase activation can be inhibited by excess p13suc1, a subunit of the protein kinase. Here we have demonstrated that affinity-purified cdc2 from Xenopus prophase oocytes may be activated in vitro by exposure to potato acid phosphatase. In vitro, excess p13 does not inhibit tyrosine dephosphorylation of prophase cdc2, but nonetheless binds and prevents the activation of the enzyme. By contrast, fully activated enzyme from metaphase Xenopus eggs is insensitive to excess p13. These observations define a p13-sensitive state in the activation of fully active cdc2 that follows tyrosine dephosphorylation.
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PMID:Direct activation of cdc2 with phosphatase: identification of p13suc1-sensitive and insensitive steps. 216 87

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

M-Phase specific protein kinase or cdc2 protein kinase is a component of MPF (M-Phase promoting factor). During meiotic maturation of Xenopus oocytes, cdc2 protein kinase is activated in correlation with MPF activity. A protein phosphorylation cascade takes place involving several protein kinases, among which casein kinase II, and different changes associated with meiosis occur such as germinal vesicle breakdown, chromosome condensation, cytoskeletal reorganization and increase in protein synthesis. Our results provide a biochemical link between cdc2 protein kinase and protein synthesis since they show that the kinase phosphorylates in vitro a p47 protein identified as elongation factor EF1 (gamma subunit) and that the in vitro site of p47 corresponds to the site phosphorylated in vivo. Immunofluorescence showed that the elongation factor (EF1-beta gamma) is localized in the oocyte cortex. Furthermore, they show that cdc2 kinase phosphorylates and activates casein kinase II in vitro, strongly supporting the view that casein kinase II is involved in the phosphorylation cascade originated by cdc2 kinase.
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PMID:Protein phosphorylation during meiotic maturation of Xenopus oocytes: cdc2 protein kinase targets. 220 50

The nuclear envelope is a dynamic structure that completely disassembles in response to MPF/cdc2 activity in mitosis. A key feature of this process is the hyperphosphorylation of the major structural proteins of the envelope, the nuclear lamins A, B, and C. Two highly conserved serine residues of the lamin protein (Ser-22 and Ser-392 of lamins A and C) are symmetrically positioned 5 amino acids from the ends of the large alpha-helical domain and are shown in the accompanying paper by Ward and Kirschner to be among four sites phosphorylated during nuclear envelope breakdown. Mutations in Ser-22 and Ser-392 that prevent phosphorylation at these sites block the disassembly of the nuclear lamina during mitosis. We propose a model for the regulation of lamin assembly in which phosphorylation just outside the ends of the alpha-helical domain controls the assembly dynamics of the lamin coiled-coil dimers.
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PMID:Mutations of phosphorylation sites in lamin A that prevent nuclear lamina disassembly in mitosis. 234 12

We have purified to near homogeneity the M-phase-specific protein kinase from starfish oocytes at first meiotic metaphase, using an improved procedure based on affinity chromatography on the immobilized yeast protein suc1. As already reported, this is identical to MPF, the cytoplasmic factor that controls entry of eukaryotic cells into M-phase. MPF is a complex formed by the stoichiometric association of a 34-kd polypeptide previously identified as cdc2 with a polypeptide that migrates with the same mobility as starfish cyclin in SDS-PAGE (apparent mol. wt 47 kd). A cDNA clone encoding starfish cyclin B has been isolated and its sequence determined. It contains a single open reading frame encoding a predicted 43 729-dalton protein. Partial microsequencing of the 47-kd polypeptide component of MPF allowed its identification as the starfish cyclin. Since the apparent mol. wt of native starfish MPF was found to be less than 100 kd, it is a heterodimer comprising one molecule of cdc2 and one molecule of cyclin B.
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PMID:MPF from starfish oocytes at first meiotic metaphase is a heterodimer containing one molecule of cdc2 and one molecule of cyclin B. 253 Oct 73

In Xenopus, a cytoplasmic agent known as MPF induces entry into mitosis. In fission yeast, genetic studies have shown that the cdc2 kinase regulates mitotic initiation. The 13 kd product of the suc1 gene interacts with the cdc2 kinase in yeast cells. We show that the yeast suc1 gene product (p13) is a potent inhibitor of MPF in cell-free extracts from Xenopus eggs. p13 appears to exert its antagonistic effect by binding directly to MPF. MPF activity is quantitatively depleted by chromatography on a p13 affinity column. Concomitantly, the Xenopus counterpart of the yeast cdc2 protein is adsorbed to the column. A 42 kd protein also binds specifically to the p13 affinity matrix. These findings suggest that the Xenopus cdc2 protein and the 42 kd protein are components of MPF.
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PMID:The Xenopus cdc2 protein is a component of MPF, a cytoplasmic regulator of mitosis. 329 2

Brefeldin A, a fungal metabolite which disrupts protein traffic, provokes indirect activation of cdc2 protein kinase in Xenopus oocytes. Cdc2 protein kinase activation was judged by MPF (M-phase factor) transfer activity, histone H1 kinase activity, and phosphorylation in vivo of the guanine-nucleotide exchange complex EF-1 beta gamma delta. Oocytes resumed complete meiosis upon brefeldin A treatment. Cdc2 protein kinase, MAP kinase, cyclin B, MPF, and protein synthesis changes were all comparable in brefeldin A-treated oocytes and in progesterone-induced oocytes. ED50 for brefeldin A was 0.6 microM. Brefeldin A activation of cdc2 protein kinase occurs with a long time course. Simultaneous treatment of the oocytes at a subthreshold concentration of 1 nM progesterone and 30 microM brefeldin A considerably shortened the kinetics of maturation. Brefeldin A induction of maturation was sensitive to drugs that act on cAMP metabolism. ID50 for IBMX was 0.1 mM, compared to 1 mM for progesterone-treated oocytes. Brefeldin A inhibited protein traffic in oocytes as determined from protein export experiments. ID50 was between 0.1 and 1 microM. Our results give new insights into the possible mechanism of induction of meiotic maturation and further demonstrate that brefeldin A acts on cell cycle regulatory elements.
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PMID:Brefeldin A provokes indirect activation of cdc2 kinase (MPF) in Xenopus oocytes, resulting in meiotic cell division. 754 76

This chapter has briefly reviewed the current status of investigations on the hormonal regulation of oocyte growth and maturation in fish (see Figs. 4 and 9). Pituitary gonadotropins are of primary importance in triggering these processes in fish oocytes. In both cases, however, the actions of gonadotropins are not direct, but are mediated by the follicular production of steroidal mediators, estradiol-17 beta (oocyte growth) and 17 alpha,20 beta-DP or 20 beta-S (oocyte maturation). Investigators have established that both estradiol-17 beta and 17 alpha,20 beta-DP are biosynthesized by salmonid ovarian follicles via an interaction of two cell layers, the thecal and granulosa cell layers (two-cell-type model). The granulosa cell layers are the site of production of these two steroidal mediators, but their production depends on the provision of precursor steroids by the thecal cell layers. A distinct steroidogenic shift from estradiol-17 beta to 17 alpha,20 beta-DP, occurring in salmonid ovarian follicles immediately prior to oocyte maturation, is a prerequisite for the growing oocytes to enter the maturation stage, and requires a complex and integrated network of gene regulation involving cell specificity, hormonal regulation, and developmental patterning. The cDNAs for most of the steroidogenic enzymes responsible for estradiol-17 beta and 17 alpha,20 beta-DP biosynthesis have been cloned from rainbow trout ovaries. Our next task is to determine how gonadotropin and other factors act on ovarian follicle cells to turn the expression of these specific genes on and off at specific times during oocyte growth and maturation. Increasing evidence now suggests that a variety of neuromodulatory, autocrine, and paracrine factors may also be involved in the regulation of steroidogenesis in fish ovarian follicles. Molecular biological technologies should be applied to identify these substances. Of considerable interest is the finding that MIH, unlike most steroid hormones, acts on its receptors at the surface of oocytes. Further studies of the association of the MIH-MIH receptor complex with a Gi protein, probably resulting in the inactivation of adenylate cyclase, should lead to a discovery of a new mechanism of steroid hormone action. The early steps following MIH action involve the formation of the major cytoplasmic mediator of MIH, MPF. Fish MPF, like that of Xenopus and starfish, consists of two components: cdc2 kinase and cyclin B. Nevertheless, the mechanism of MIH-induced MPF activation in fish oocytes differs from that in Xenopus and starfish because the appearance of cyclin B protein is a crucial step for 17 alpha,20 beta-DP-induced oocyte maturation in fish.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of oocyte growth and maturation in fish. 755 44

A few years after the identification of cyclin B-cdc2 kinase as the universal factor that controls onset of M-phase in eukaryotic cells, MPF (M-phase promoting factor), it became evident that all transitions of the cell cycle are controlled through phosphorylation of specific targets due to changes in the activity of a variety of cyclin-dependent kinases (cdks). These transitions include conversion of quiescent cells to a state of active proliferation, commitment to DNA replication, initiation of DNA replication, and entry into and exit from mitosis. Changes in the activity of cdks along the cell cycle depend not only on their association with a variety of cyclins (including G1/S and G2/M cyclins) and on posttranslational modifications by phosphorylation-dephosphorylation reactions, but also on specific protein inhibitors and on protein degradation.
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PMID:The cyclin-dependent protein kinases and the control of cell division. 795 16


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