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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 p34 protein kinase encoded by the cdc2 gene is a key component of the eukaryotic cell cycle required for the G1- to S-phase transition and entry into mitosis. To study the regulation of plant meristem activity and cell proliferation, we have examined the tissue-specific accumulation of cdc2 transcripts in Arabidopsis thaliana and the related crucifer radish (Raphanus sativus) by in situ hybridization using A. thaliana cdc2 cDNA sequences as a probe. cdc2 transcripts accumulated in leaf primordia and within the vegetative shoot apical meristem. During flower development, high levels of expression were observed in meristems, in the basal regions of developing organs, in the developing vasculature, and associated with rib meristems elaborated late in the development of some floral organs. In root tips, cdc2 transcripts accumulated in the meristematic region and adjacent daughter cells but were not detected in the quiescent center. There was strong hybridization throughout the pericycle, and a further localized accumulation of cdc2 transcripts was observed in the initial stages of the activation of a new meristem at sites of lateral root development. We conclude that cdc2 expression is a critical factor in the regulation of meristem activity and establishment of proliferative competence.
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PMID:Spatial pattern of cdc2 expression in relation to meristem activity and cell proliferation during plant development. 150 45

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 number of low molecular weight proteins have recently been identified that specifically inhibit the function of cyclin-dependent protein kinases in mammalian cells. These fall into two distinct families based on primary sequence comparisons and probable modes of action. Using a simple in vitro binding assay, we show that p21CDKN1 and the related p27KIP1 can efficiently interact with cyclins D1, D2, D3, E and A, and to a lesser extent with cyclin B. By generating a deleted form of cyclin D1 that binds to p21 and p27 but not to Cdks, we confirm that these interaction do not depend on stoichiometric amounts of the relevant kinase subunit. Moreover, p21 and p27 do not detectably associated with kinase subunits unless a cyclin is present. This is in sharp contrast to the properties of p16CDKN2 and p15MTS2/INK4b which bind to Cdk4 and Cdk6 in the absence of any cyclin. These data suggest that p21 and p27 act as broad spectrum regulators of cyclin dependent kinase function by participating in ternary complexes whereas the p16 family specifically interfere with the formation of cyclin D-dependent kinase complexes.
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PMID:Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to cyclins. 747 82

Expression of cyclin dependent kinase cdk5 and its regulator p35 has been shown in the cytoplasm of adult neurons. Here we demonstrate that another potential regulator of cdk5, cyclin E, is expressed in the nervous system and forms complexes with cdk5. Western blot analyses identifies expression of two forms of cyclin E in the mouse nervous system with the 56 kDa form mainly expressed in neurons and 51 kDa form expressed in astrocytes and oligodendrocytes.
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PMID:Cyclin E is expressed in neurons and forms complexes with cdk5. 766 93

Transcription factor E2F-1 has a putative consensus sequence for phosphorylation by cyclin dependent kinase (Ser-Pro-X-Lys/Arg). Therefore, we studied the phosphorylation of E2F-1 in vivo and in vitro and its biological functions. E2F-1 was prepared by immunoprecipitation with anti-E2F-1 antibody from IMR32 lysates and was effectively phosphorylated by human cyclin A-cdk2 which was expressed in insect cells using baculovirus system. GST-E2F-1 was phosphorylated by cyclin A-cdk2 more efficiently than by cyclin E-cdk2. Cyclin D1-cdk4 phosphorylated pRB but scarcely phosphorylated GST-E2F-1 or H1 histone. The 60 kd protein precipitated with anti-E2F-1 antibody was phosphorylated in vivo. Phospho-peptide mapping indicated that its cleavage profile was identical with that of E2F-1 phosphorylated by cyclin A-cdk2 in vitro. This 60 kd protein, which is likely to be E2F-1, was not phosphorylated during the G0 and early G1 phase. Phosphorylation of E2F-1 began from the S phase while phosphorylation of pRB started nearly at G1/S. The in vivo phosphorylation of E2F-1 was inhibited by butyrolactone I, a cyclin-dependent kinase inhibitor (Kitagawa et al., 1993, Oncogene, 8, 2425-2432). The binding of E2F-1 to E2 promoter was found to be reduced by phosphorylation of E2F-1 by cyclin A-cdk2, suggesting that phosphorylation of E2F-1 may induce shut off of gene expression at the transcriptional level. These results suggest that E2F-1 is phosphorylated by cyclin A-cdk2 in the S phase in vivo as well as in vitro and that its phosphorylation by cyclin A-cdk2 may modulate its activity.
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PMID:Phosphorylation of E2F-1 by cyclin A-cdk2. 783 23

Proliferation of hematopoietic cells is controlled by both growth stimulatory and inhibitory cytokines acting primarily in G1, but the mechanisms which integrate these disparate signals are unknown. In a myeloid cell line dependent on interleukin-3 (IL-3) for proliferation, expression of the cyclin dependent kinase Cdk4 and D-type cyclin partners, D2 and D3, in mid G1 was found to be directly related to the concentration of IL-3. TGF beta 1, which induces cell cycle arrest in mid-G1, blocked IL-3-induced expression of Cdk4, but had no effect on expression of cyclins D2 or D3. Sublines made to constitutively express Cdk4, but not lines constitutively expressing cyclins D2 or D3, were hyper responsive to IL-3 and resistant to TGF beta 1. Using an in vitro kinase assay with recombinant retinoblastoma protein (Rb) as a substrate, cyclin D2-associated kinase activity was shown to be induced in G1 by IL-3 and inhibited by TGF beta 1. Constitutive expression of Cdk4, but not cyclin D2 or D3, increased cyclin D2-associated Rb kinase activity and this activity could no longer be inhibited by TGF beta 1. Also, in vivo phosphorylation of Rb was inhibited by TGF beta 1 in wild type but not in Cdk4 lines. Cdk2 kinase activity was also decreased by TGF beta 1, and restored by overexpression of Cdk4. These results implicate Cdk4 activity as a mid G1 checkpoint sensitive to both growth stimulatory and inhibitory cytokines.
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PMID:Cdk4 integrates growth stimulatory and inhibitory signals during G1 phase of hematopoietic cells. 786 52

Numerous studies have been published these last few years on the involvement of MAP kinases in signal transduction reflecting their importance in cell cycle and cell growth controls. The identification and the characterization of their direct upstream activator has considerably enlarged our understanding of the phosphorylation network. The MAP kinase kinases (MAPKKs) are dual-specificity protein kinases which phosphorylate and activate MAP kinases. To date, MAPKK homologues have been found in yeast, invertebrates, amphibians, and mammals. Moreover, the MAPKK/MAPK phosphorylation switch constitutes a basic module activated in distinct pathways in yeast and in vertebrates. MAPKK regulation studies have led to the discovery of at least four MAPKK convergent pathways in higher organisms. One of these is similar to the yeast pheromone response pathway which includes the ste11 protein kinase. Two other pathways require the activation of either one or both of the serine/threonine kinase-encoded oncogenes c-Raf-1 and c-Mos. Additionally, recent studies suggest a possible effect of the cell cycle control regulator cyclin-dependent kinase 1 (cdc2) on MAPKK activity. Finally, MAPKKs seem to be essential transducers through which signals must pass before reaching the nucleus.
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PMID:MAP kinase kinase: a node connecting multiple pathways. 800 6

The reproductive cycle in eukaryotic cells is partly controlled by the p34 protein kinase, the product of the cdc2 gene. We report here the tissue reactivity of four new anti-cdc2 monoclonal antibodies in relation to the known proliferation markers Ki-67 and JC1. In tissues where proliferation occurs, germinal centres in the tonsil, basal layers of tonsular epithelium and skin, cortex of the thymus, seminiferous tubules of the testis and epithelium of the colon, the anti-cdc2 antibodies gave positive nuclear staining as did the proliferation markers. The percentage of positive cells was, however, lower with the cdc2 antibodies. Given the role of the cdc2 gene at specific points of the cell cycle, these antibodies are potentially useful as markers of different phases of the cell cycle and may help to detect abnormalities in cell cycle control in disease.
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PMID:Distribution of the cdc2 gene product in normal tissues: an immunocytochemical study using four new monoclonal antibodies. 804 23

The Fos family of transcription factors, c-Fos, FosB, Fra-1 and Fra-2, are rapidly induced in quiescent fibroblasts following serum or growth factor stimulation. The Fos proteins show distinct patterns of expression during cell growth with only Fra-1 and Fra-2 maintained at significant levels in growing cells, suggesting that the different family members direct unique functions for cell growth. Post-translational modification of Fos proteins has been observed following serum stimulation, which may allow an additional level of regulation. Our studies show that the synthesis and post-translational modification of Fra-1 and Fra-2 in Swiss 3T3 cells is serum-dependent during G1 following the transition from G0 and during asynchronous growth but is serum-independent during S phase and mitosis. Post-translational modification of Fra-1 and Fra-2 causes a significant shift in their gel mobility which is eliminated by alkaline phosphatase treatment. Several kinases can phosphorylate Fra-1 and Fra-2 in vitro, including cAMP-dependent kinase (PKA), protein kinase C (PKC), cyclin-dependent kinase 1-cdc2 (cdc2), and mitogen activated protein (MAP) kinase. From these, MAP kinase is the only one that causes a shift in gel mobility similar to that observed in vivo. One dimensional phosphopeptide maps of Fra-1 and Fra-2 phosphorylated by MAP kinase in vitro are similar to those of in vivo labeled Fra-1 and Fra-2, suggesting that MAP kinase may also phosphorylate Fra-1 and Fra-2 in vivo. We have also determined that phosphorylation of Fra-1 and Fra-2 by MAP kinase increases their DNA binding activity.
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PMID:Regulation of Fra-1 and Fra-2 phosphorylation differs during the cell cycle of fibroblasts and phosphorylation in vitro by MAP kinase affects DNA binding activity. 805 17

Cyclin B, a positive regulatory subunit of the cdc2 protein kinase complex, is synthesized across the cell cycle and then rapidly degraded at the end of mitosis. Degradation of cyclin B is triggered by increased levels of active cdc2 and is required for exit from mitosis. It was shown previously that cyclin degradation is carried out by the ubiquitin system, but the components responsible for the specificity and regulation of cyclin-ubiquitin ligation have not been identified. The formation of ubiquitin-protein conjugates usually requires the sequential action of three enzymes: a ubiquitin-activating enzyme (E1), a ubiquitin-carrier protein (E2), and a ubiquitin-protein ligase (E3). In this work we employed a fractionation approach to identify the components of a clam oocyte system responsible for specific ubiquitination of cyclin and to determine which components are regulated by cdc2. Experimental conditions were established under which a fusion protein containing an amino-terminal fragment of cyclin B is ligated to ubiquitin only in extracts from M-phase but not from interphase cells. Fractionation of M-phase extracts by DEAE-cellulose and high speed centrifugation yielded three fractions that were all required for cell cycle stage-specific cyclin-ubiquitin ligation. Only one of these fractions could be replaced by a previously known enzyme of the ubiquitin system, E1. A second fraction contained a novel species of E2, termed E2-C, which acts in the ligation of ubiquitin to cyclin but not to other endogenous proteins. A third component is associated with particulate material. Whereas E2-C from either M-phase or interphase extracts is active, the particulate component is active only in M-phase. Incubation of the particulate fraction from interphase cells with the protein kinase cdc2 activates it for cyclin-ubiquitin ligation, after a lag of about 30 min. These findings suggest that the particulate fraction may contain an E3 enzyme that acts on cyclin, as well as additional factors activated by cdc2.
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PMID:Components of a system that ligates cyclin to ubiquitin and their regulation by the protein kinase cdc2. 810 68


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