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)

We studied enzymatic activities in sea urchin egg extracts that phosphorylate myosin regulatory light chain (MRLC) from chicken gizzard smooth muscle. The activity in the presence of EGTA showed cell cycle-dependent changes similar to that of histone H1 kinase, namely, it peaked shortly before cleavage, while that in the presence of Ca2+ ions did not show significant change during division cycle. Phosphopeptide mapping revealed that both the sites phosphorylatable by smooth muscle myosin light chain kinase (MLCK sites) and the sites phosphorylatable by protein kinase C (PKC sites) were phosphorylated in the presence or absence of Ca2+ ions. By analyses using an inhibitor of cdc2 kinase, butyrolactone-I, and ion exchange column chromatography, at least three kinases were detected as kinases that phosphorylate MRLC in vitro. These kinases phosphorylated distinct sites on MRLC. The first one, which phosphorylated the PKC sites, was identified as cdc2 kinase. The second one phosphorylated the MLCK sites in the absence of Ca2+ ions. The third one phosphorylated unknown sites. Possible implication of these activities in regulation of cytokinesis is discussed.
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PMID:Cell cycle-dependent phosphorylation of smooth muscle myosin light chain in sea urchin egg extracts. 879 90

Activation of the latent DNA binding function of human p53 protein by the bacterial Hsp70, DnaK, represents a unique reaction in which a heat shock protein can interact with a native protein to affect its function. We have localized a likely DnaK interaction site on native human p53 tetramers to a motif flanking the COOH-terminal casein kinase II and protein kinase C phosphorylation sites. Murine p53 is less efficiently activated by DnaK, which has permitted a search for factors that might cooperate in p53 activation by DnaK. We show that optimal activation by DnaK may be dependent upon the phosphorylation state of murine p53, in particular, modification of p53 at the cdc2 phosphorylation site by point mutation decreases the extent of activation by DnaK. Additionally, the monoclonal antibody PAb241, binding in the vicinity of the cdc2 phosphorylation site, is able to activate the specific DNA binding function of p53. This has led us to propose a second regulatory motif flanking the tetramerization domain of p53 that cooperates with factors binding at the negative regulatory domain in the extreme COOH terminus.
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PMID:Modification of two distinct COOH-terminal domains is required for murine p53 activation by bacterial Hsp70. 894 78

UCN-01 (7-hydroxyl-staurosporine) was originally isolated as a Ca2+- and phospholipid-dependent protein kinase C selective inhibitor and now is being developed as an anticancer agent. Results from our and other laboratories have suggested that UCN-01 induces preferential G1-phase accumulation in several human tumor cell lines tested. To elucidate this mechanism, we examined the effects of UCN-01 on several cell cycle-regulatory proteins critical for G1-S-phase transition in p53-mutated human epidermoid carcinoma A431 cells. After 24 h exposure at around 50% growth-inhibitory concentrations (IC50s), 260 and 520 nM, UCN-01 induced the accumulation of pRb (the dephosphorylated retinoblastoma protein form). The protein expression of cyclin A but not cyclin E was markedly reduced and that of cyclin D1 was partially reduced under the same condition. UCN-01 also showed the concentration-dependent inhibitions of the activity of cyclin-dependent kinase 2 (CDK2) using histone H1 and pRb as substrates in vitro (IC50, 530 and 640 nM, respectively). In addition, CDK2 activities of the cells pretreated with UCN-01 for 24 h at 260 and 520 nM were markedly inhibited, giving IC50s of far less than 260 nM. When the same cell lysates were analyzed by Western blotting for CDK2, the lower band (e.g., active and phosphorylated CDK2) was remarkably reduced, in accordance with the reduced activity. Furthermore, UCN-01 induced the expression of the CDK inhibitor p21 protein and its complex formation with CDK2 after 24 h exposure at 260 and 520 nM, whereas the expression level was very low or undetectable in untreated or DNA-damaged cells. The increase of p21 mRNA levels was also induced under the same condition. UCN-01 further increased luciferase activities in A431 cells transiently transfected with p21 promoter-luciferase reporter plasmid after 24 h exposure at 260 and 520 nM. UCN-01 also increased the expression of the CDK inhibitor p27 protein after 24 h exposure at 260 and 520 nM. These results suggest that G1-phase accumulation induced by UCN-01 is associated with dephosphorylation of Rb and CDK2 proteins as well as induction of CDK inhibitors p21 and p27.
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PMID:G1 phase accumulation induced by UCN-01 is associated with dephosphorylation of Rb and CDK2 proteins as well as induction of CDK inhibitor p21/Cip1/WAF1/Sdi1 in p53-mutated human epidermoid carcinoma A431 cells. 910 51

Amyloid precursor-like proteins (APLPs), APLP1 and APLP2, are members of a gene family which include the Alzheimer beta-amyloid precursor protein (APP). APLP1, APLP2, and APP contain highly homologous amino acid sequences, especially in their cytoplasmic domains, although APLPs lack the beta-amyloid domain derived by proteolytic processing from APP. APP is phosphorylated at three sites in the cytoplasmic domain in cultured cells and adult rat brain [Suzuki et al. (1994) EMBO J. 13, 1114-1122; Oishi, et al. (1997) Mol. Med. 3, 109-121] and at sites in the extracellular domain in cultured cells [Knops et al. (1993) Biochem. Biophys. Res. Commun. 197, 380-385; Hung & Selkoe (1994) EMBO J. 13, 534-542; Walter et al. (1997) J. Biol. Chem. 272, 1896-1903]. We report here that a cytoplasmic domain peptide from APLP1 is phosphorylated in vitro by protein kinase C and that a cytoplasmic domain peptide from APLP2 is phosphorylated in vitro by protein kinase C and cdc2 kinase. APLP2 is phosphorylated by cdc2 kinase at a site homologous to the cdc2 kinase site phosphorylated in APP. Furthermore, phosphorylation of this site occurs in a cell cycle-dependent manner in cultured cells. These findings indicate that in intact cells the phosphorylation of APLP2 appears to be regulated in a similar fashion to that of APP.
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PMID:Phosphorylation of Alzheimer beta-amyloid precursor-like proteins. 910 75

A monoclonal antibody, CML-1, raised against carrot (Daucus carota L.) nuclear-matrix proteins selectively labeled the nuclear periphery of carrot protoplasts when visualized by confocal and electron microscopy. To identify the constituent proteins of higher plant cells structurally homologous to the vertebrate nuclear lamina, we cloned overlapping cDNAs partially encoding a CML-1-recognized protein and determined the entire sequence including the open reading frame. When the deduced amino acid sequence was compared with other known protein sequences contained in major databases, no protein was found to show high sequence identity across the whole region of the protein, while the partial sequence showed strong similarities with myosin, tropomyosin, and some intermediate filament proteins. The protein, designated NMCP1, had an estimated molecular mass of 133.6 kDa and showed three characteristic domains. The central domain contains long alpha-helices exhibiting heptad repeats of apolar residues, demonstrating structural similarity to that of filament-forming proteins. The terminal domains are predominantly nonhelical and contain potential sequence motifs for nuclear localization signals. NMCP1 has many recognition motifs for different types of protein kinases, including cdc2 kinase and PKC. These results suggest that NMCP1 protein forms coiled-coil filaments and is a constituent of the peripheral architecture of the higher plant cell nucleus.
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PMID:Peripheral framework of carrot cell nucleus contains a novel protein predicted to exhibit a long alpha-helical domain. 914 34

This paper reviews the mechanism of sex hormone actions on the thymus, presenting mainly our data obtained at the cellular and molecular levels. First, data supporting the "genomic" action via the nuclear sex hormone receptor complexes are as follows: 1) sex hormone receptors and the thymic factor (thymulin) are co-localized in thymic epithelial cells, but not in T cells; 2) production/expression of thymic factors (thymulin, thymosin alpha 1) are remarkably inhibited by sex hormone treatment; 3) sex hormones cause changes in T cell subpopulations in the thymus; and 4) sex hormones strongly influence the development of thymus tumors in spontaneous thymoma BUF/Mna rats through their receptor within the tumor cells. Secondly, data indicating the "non-genomic" action of sex hormones via a membrane signal-generating mechanism are as follows: 1) the proliferation/maturation of thymic epithelial cells is mediated through protein kinase C activity introduced by sex hormones; 2) sex hormones directly influence DNA synthesis and cdc2 kinase (cell cycle-promoting factor) activity.
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PMID:Sex hormones and the thymus in relation to thymocyte proliferation and maturation. 916 87

It is generally recognized that bcl-2 gene strongly protects cells from apoptosis in various situations. But its function is still to be examined. We analyzed the effect of bcl-2 gene using growth factor dependent cell line, TF-1, derived from an erythroleukemia patient. On GM-CSF removal TF-1 (bcl-2) cells which were transfected with bcl-2 cDNA by retrovirus vector system survived and arrested in G0-1 phase of the cell cycle, while TF-1 (mock) cells which were transfected with vector only also arrested in G0-1 but decreased in number in several days and showed typical apoptosis. N-acetylcysteine, one of antioxidants, did not show such anti-apoptotic effect as bcl-2 in the preincubation experiment. By centrifugal elutriation system the G0-1 arrested subfraction of TF-1 (bcl-2) showed time delay at the re-entry into cell after GM-CSF re-addition when compared with the G0-1 arrested subfraction of TF-1 (mock). Similar delay in cell cycle progression was observed after 24hs-exposure of staurosporine, a protein kinase C (PKC) inhibitor. The expression of cell cycle genes including cyclin A, C, D1, E, cdk2, 4, c-myc, bax and bcl-x showed no difference between these two cell lines upon growth factor removal. These results imply that the functional commitment of bcl-2 into cell cycle progression under the situation of apoptosis especially at the restriction point of G1-S transition.
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PMID:[Overexpression of bcl-2 suppresses apoptosis in the human leukemia cell line TF-1]. 925 8

Disassembly of the sperm nuclear envelope at fertilization is one of the earliest events in the development of the male pronucleus. We report that nuclear lamina disassembly in interphase sea urchin egg cytosol is a result of lamin B phosphorylation mediated by protein kinase C (PKC). Lamin B of permeabilized sea urchin sperm nuclei incubated in fertilized egg G1 phase cytosolic extract is phosphorylated within 1 min of incubation and solubilized prior to sperm chromatin decondensation. Phosphorylation is Ca2+-dependent. It is reversibly inhibited by the PKC-specific inhibitor chelerythrine, a PKC pseudosubstrate inhibitor peptide, and a PKC substrate peptide, but not by inhibitors of PKA, p34(cdc2) or calmodulin kinase II. Phosphorylation is inhibited by immunodepletion of cytosolic PKC and restored by addition of purified rat brain PKC. Sperm lamin B is a substrate for rat brain PKC in vitro, resulting in lamin B solubilization. Two-dimensional phosphopeptide maps of lamin B phosphorylated by the cytosolic kinase and by purified rat PKC are virtually identical. These data suggest that PKC is the major kinase required for interphase disassembly of the sperm lamina.
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PMID:Protein kinase C-mediated interphase lamin B phosphorylation and solubilization. 926 Nov 38

We present here the nucleotide sequence for a cDNA clone encoding p34cdc2 from sea urchin, Hemicentrotus pulcherrimus. The obtained cDNA comprised 301 amino acid residues that contained the PSTAIRE domain to be important for binding to cyclins. Amino acid sequence similarity between this clone and other eukaryotic cdc2 sequences averaged approximately 72%. Using p13suc1-conjugated Sepharose 4B and a selective inhibitor of p34cdc2 kinase, butyrolactone I, it was first suggested that p34cdc2 kinase is involved in the phosphorylation of MRLC at both MLCK site and two PKC sites.
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PMID:Identification of p34cdc2 kinase from sea urchin Hemicentrotus pulcherrimus and its involvement in the phosphorylation of myosin II regulatory light chain in the metaphase extract. 937 Mar 2

Phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] has been known to bind to the pleckstrin homology domain and the phosphotyrosine-binding domain as well as actin-binding proteins, and to regulate their functions. We have tried to find new PtdIns(4,5)P2-binding proteins and to clarify the physiological effects of PtdIns(4,5)P2 on their function. We report here that histones H1 and H3 are PtdIns(4,5)P2-binding proteins which were identified using antibodies specific to PtdIns(4,5)P2, H1, and H3. This binding was further confirmed by extracting PtdIns(4,5)P2 from purified histone H1 and H3. Furthermore, the binding site of PtdIns(4,5)P2 in histone H1 was found in the carboxyl-terminal 103 amino acids. It was also shown that the amounts of PtdIns(4,5)P2 bound to H1 decrease when histone H1 is phosphorylated by protein kinase C but not by protein kinase A or cdc2 kinase, in vitro. The protein kinase C phosphorylation site is localized close to the PtdIns(4,5)P2-binding site, suggesting that phosphorylation of histone H1 by protein kinase C interferes stereostructurally with PtdIns(4,5)P2 binding. We further noticed that PtdIns(4,5)P2 binding to H1 counteracts the histone H1-mediated repression of basal transcription by RNA polymerase II in a Drosophila transcription system in vitro. Phosphatidylinositol 4-phosphate and phosphatidylinositol 3,4,5-trisphosphate affect this transcription activity more weakly than PtdIns(4,5)P2, but PtdIns and other acidic lipids have no effect on this activity. These data indicate that PtdIns(4,5)P2 bound to nuclear protein histone H1 may contribute to the regulation of transcription in eukaryotic cells.
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PMID:Phosphatidylinositol 4,5-bisphosphate reverses the inhibition of RNA transcription caused by histone H1. 949 95


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