Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Synaptonemal complexes (SCs) are structures that are formed between homologous chromosomes during meiotic prophase. They are probably involved in chromosome pairing and recombination. Using a monoclonal anti-SC antibody we isolated cDNAs encoding a major component of SCs which is localized specifically in synapsed segments of meiotic prophase chromosomes. The protein predicted from the nucleotide sequence of a full-length cDNA, named SCP1, consists of 946 amino acid residues and has a molecular weight of 111 kDa. It shares several features with nuclear lamins and some recently identified nuclear matrix proteins. The major part of SCP1 consists of long stretches capable of forming amphipathic alpha-helices. This region shows amino acid sequence similarity to the coiled-coil region of myosin heavy chain. A leucine zipper is included in this region. The carboxy-terminus has two small basic domains and several S/T-P-X-X motifs, which are characteristic of DNA-binding proteins. One of these motifs is a potential target site for p34cdc2 protein kinase. The amino-terminus is acidic and relatively proline-rich, but does not contain the S/T-P-X-X motif. The transcription of the gene encoding SCP1 is restricted to zygotene-diplotene spermatocytes. A polyclonal antiserum raised against the fusion protein of one of the cDNA clones recognizes a single protein on Western blots of isolated SCs, with an electrophoretic mobility identical to that of the antigen recognized by the original monoclonal antibody (mAb), IX5B2. From a detailed comparison of the immunogold labelling of rat SCs by mAb IX5B2 and the polyclonal anti-fusion protein antiserum respectively, we tentatively infer that the carboxy-terminus of SCP1 is orientated towards the lateral elements and that the other domains of the protein extend towards the central region between the lateral elements. We conclude that SCP1 is the major component of the transverse filaments of SCs, and speculate that it has evolved by specialization of a nuclear matrix protein.
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PMID:A coiled-coil related protein specific for synapsed regions of meiotic prophase chromosomes. 146 29

Numatrin, a nuclear matrix protein has been implicated to be involved in mitogenesis of normal and malignant cells (Feuerstein and Mond, J. Biol. Chem. 262, 11389, 1987) and was later found to be identical to the nuclear phosphoprotein, B23. To study whether phosphorylation of numatrin is regulated by mitogenic stimulation, we examined the effect of phosphorylation of numatrin in the insulin-responsive cells, NIH 3T3 HIR. We found that an increase in phosphorylation of numatrin was associated with stimulation of the cells with insulin for 4 h and that the level of phosphorylation remained elevated after 8 h. By this time there was no increase in numatrin abundance as shown by Coom-massie blue stain and Western blot analysis. The induction in phosphorylation of numatrin could not be detected after 30 min stimulation with insulin, thus, indicating that the increase in phosphorylation of numatrin is not a rapid event. Analysis of the phosphopeptides by thin layer chromatography indicated four peptides that were phosphorylated in numatrin (one major and three minor). Stimulation with insulin was associated primarily with an increase in phosphorylation of the minor phosphopeptides. The phosphopeptide map of numatrin was identical after 4, 8, 17, 24, and 32 h stimulation with insulin, indicating that identical sites are phosphorylated at different phases of the cell cycle. In a search for the protein kinase which is involved in phosphorylation of numatrin we found that numatrin is a most prominent substrate for the cell cycle regulated cdc2 (p 34) kinase. However, the major phosphopeptides which were phosphorylated by this kinase did not comigrate with either of the phosphopeptides phosphorylated in insulin-stimulated intact cells. This may indicate that it is unlikely that cdc2 kinase may account for the mechanism(s) associated with phosphorylation of numatrin by insulin under physiological conditions.
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PMID:In vivo and in vitro phosphorylation studies of numatrin, a cell cycle regulated nuclear protein, in insulin-stimulated NIH 3T3 HIR cells. 202 81

The matrix protein from avian myeloblastosis virus and the Rous sarcoma virus, Prague C strain, is a phosphoprotein. A comparison of the amino acid sequences shows these phosphoproteins are very similar. The sites of phosphorylation of the matrix protein purified from virions are identified as serine residues 68 and 106. Treatment with purified rabbit skeletal-muscle protein phosphatase 1 or 2A, selectively releases phosphate from serine 68, while alkali treatment releases phosphate from both sites. When analyzed as a substrate for six different protein kinases, only the Ca2+/phospholipid-dependent protein kinase modifies the matrix protein. The serine residues phosphorylated in vivo are identical to those phosphorylated in vitro by this protein kinase. The role of these phosphorylation events in viral production is discussed.
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PMID:Phosphorylation of avian retrovirus matrix protein by Ca2+/phospholipid-dependent protein kinase. 253 9

During cellular remodeling that accompanies cornification of epidermal cells, the highly phosphorylated protein, profilaggrin, is dephosphorylated and proteolytically cleaved to filaggrin, the keratin matrix protein. Using rat filaggrin phosphorylated by bovine casein kinase II (CK II) as a substrate, we have partially purified a phosphatase from rat epidermis which dephosphorylates rat profilaggrin in vitro. Anion exchange, hydroxylapatite, and gel filtration chromatography yielded a 100-fold purification of phosphatase from a low-salt extract. Further purification led to loss of activity; therefore, only the partially purified phosphatase was characterized. Two forms of the phosphatase, with molecular weights of approximately 170 and 40 kDa, were resolved during gel filtration. The 170-kDa form could be converted to the 40-kDa form in the presence of dithiothreitol. Both forms had pH optima of 6.6, and were strongly inhibited by NaCl (50% inhibition at 35-40 mM). Neither form hydrolyzed para-nitrophenylphosphate or dephosphorylated casein or the synthetic peptide arg3-glu3-thr-glu3, which were phosphorylated by casein kinase II. The two forms were similarly inhibited by known inorganic phosphatase inhibitors, with 22%-36% inhibition by 0.1 mM Na+/K+ tartrate, 55%-60% inhibition by 0.1 mM NaF, and 75% inhibition by 0.1 mM Na pyrophosphate. Para-chloromercuribenzoate also inhibited the activity, suggesting that reduced thiols may be important in catalysis. One mM calcium chloride altered the activity in a complex manner depending on the pH, suggesting a possible role for calcium in regulating enzyme activity.
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PMID:Characterization of an epidermal phosphatase specific for filaggrin phosphorylated by casein kinase II. 284 73

Phosphorylation of the proteins of human cytomegalovirus (CMV) virions, noninfectious enveloped particles (NIEPs), and dense bodies was investigated. Analyses of particles phosphorylated in vivo showed the following. Virions contain three predominant phosphoproteins (i.e., basic phosphoprotein and upper and lower matrix proteins) and at least nine minor phosphorylated species. NIEPs contain all of these and one additional major species, the assembly protein. Dense bodies contain only one (i.e., lower matrix) of the predominant and four of the minor virion phosphoproteins. Two-dimensional (charge-size) separations in denaturing polyacrylamide gels showed that the relative net charges of the predominant phosphorylated species ranged from the basic phosphoprotein to the more neutral upper matrix protein. In vitro assays showed that purified virions of human CMV have an associated protein kinase activity. The activity was detected only after disrupting the envelope; it had a pH optimum of approximately 9 to 9.5 and required a divalent cation, preferring magnesium to manganese. In vitro, this activity catalyzed phosphorylation of the virion proteins observed to be phosphorylated in vivo. Peptide comparisons indicated that the sites phosphorylated in vitro are a subset of those phosphorylated in vivo, underscoring the probable biological relevance of the kinase activity. Casein, phosvitin, and to a minor extent lysine-rich histones served as exogenous phosphate acceptors. Arginine-rich and lysine-rich histones and protamine sulfate, as well as the polyamines spermine and spermidine, stimulated incorporation of phosphate into the endogenous viral proteins. Virions of all human and simian CMV strains tested showed this activity. Analyses of other virus particles, including three intracellular capsid forms (i.e., A, B, and C capsids), NIEPs, and dense bodies, indicated that the active enzyme was not present in the capsid. Rate-velocity sedimentation of disrupted virions separated the protein kinase activity into two fractions: one that phosphorylated exogenous casein and another that phosphorylated primarily the endogenous virion proteins.
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PMID:Characterization of phosphoproteins and protein kinase activity of virions, noninfectious enveloped particles, and dense bodies of human cytomegalovirus. 301 33

Despite the extensive literature on the biological actions of Ca2+ and calmodulin, very little is known about their involvement in nuclear functions, e.g., regulation of specific gene expression. To date, the only genes other than prolactin and growth hormone shown to be regulated by perturbations in cell Ca2+ are those coding for two glucose-regulated proteins. However, there is a growing body of indirect evidence for nuclear functions of Ca2+ and calmodulin, and we suspect that other examples of Ca2+-regulated genes will emerge. We have described in this chapter several different experimental approaches which we have employed to examine first whether prolactin gene expression is regulated by changes in cell Ca2+ content, and then to begin searching for the components of the mechanism by which Ca2+ exerts its effects on the prolactin gene. The tentative identification of 56-kDa nuclear matrix protein as both a calmodulin-binding protein and a substrate of a Ca2+-calmodulin-dependent protein kinase suggests that NMP 56 may be a subunit of a multifunctional Ca2+-calmodulin-protein kinase. This enzyme was recently detected in the nuclear matrix fraction of neuronal nuclei, and was shown to phosphorylate a chromatin protein similar to high mobility group protein 17 (HMG 17). Since HMG 17 is associated with actively transcribed chromatin, its phosphorylation in GH3 cells might play a role in the Ca2+-calmodulin-dependent regulation of prolactin gene expression by hormones and growth factors.
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PMID:Ca2+/calmodulin regulation of prolactin gene expression. 358 41

Nuclear matrix was isolated from cultured human fibroblasts by extraction of nuclei with 2 M NaCl. Electron microscopic observation on the isolated nuclear matrix revealed a fine network structure. The matrix fraction contained approximately 15% of total nuclear DNA and the matrix DNA was about 3- to 4-fold enriched in transcriptionally active collagen I (alpha 2) gene sequences, whereas transcriptionally inactive beta-globin gene sequences were not enriched. The nuclear matrix contained two major proteins of 65,000 and 45,000 daltons (pI 5.9 and 5.6, respectively). The DNA-binding activity of these nuclear matrix proteins was examined by Western blotting or by nitrocellulose filter-binding assay using cloned specific gene probes. The results suggest that there is no base sequence specificity in the binding, and that protein species of 60,000 to 200,000 daltons showed DNA-binding activity. These results indicate that association of transcribing genes with the nuclear matrix may reflect the functional state of the genes and may not be determined solely by the base sequence specificity of DNA binding. The nuclear matrix protein of 65,000 daltons was phosphorylated in vivo, and was the main substrate for protein kinase(s) associated with the nuclear matrix.
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PMID:Characterization of nuclear matrix from cultured normal human fibroblasts. 371 Oct 68

Evidence is presented that the nuclear matrix is a cell-cycle-dependent site of increased intranuclear protein phosphorylation. The incorporation of radioactive phosphate (32P) is highest during the premitotic (G2) phase and 40-50% less in the postmitotic phase (G1). This is observed for both total matrix protein and for several individual polypeptides ranging in molecular mass from greater than 200 kDa to 19 kDa. The phenomenon can be demonstrated when the matrix is isolated from orthophosphate-labeled intact cells, as well as when the matrix is isolated and then incubated in vitro in a protein kinase reaction mixture. The ability of the isolated matrix to mimic the events in vivo indicates the presence of endogenous protein phosphokinase activity and physiological substrates in this isolated nuclear fraction. Further evidence for such mimicry was obtained when amino acid phosphorylation sites were determined. Phosphoserine is the most abundant phosphoamino acid in the matrix labelled both in vitro and in vivo, although phosphothreonine and phosphotyrosine are also present. On the basis of several pieces of data, the endogenous matrix activity appears to be due to multiple protein phosphokinases. Since the maximum phosphorylation coincides with premitosis, the phosphoproteins may play a role in mitotic events. These observations extend and expand the application of this fraction to the study of nuclear structure/function relationships, particularly at the time of mitosis.
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PMID:Nuclear matrix: a cell-cycle-dependent site of increased intranuclear protein phosphorylation. 685 29

Differentiating chick limb-bud mesenchymal cells plated in micromass culture form a cartilage matrix that can be mineralized in the presence of 4 mM inorganic phosphate (Pi), and 1 mM calcium. Previous studies showed that when beta-glycerophosphate (beta GP) is used in place of Pi, the mineral crystals formed are larger and differ in distribution. The present study shows that the difference in distribution is not associated with alterations in cell proliferation, protein synthesis, or with collagen, proteoglycan core protein, or alkaline phosphatase gene expression. Cultures with 2.5, 5, and 10 mM beta GP did show different levels of alkaline phosphatase activity, and in the presence of low (0.3 mM) Ca had different Pi contents (4, 6 and 9 mM, respectively), indicating that the increase in CaxP product may in part be responsible for the altered pattern of mineralization. However, cultures with beta GP in which alkaline phosphatase activity was inhibited with levamisole still had an altered mineral distribution as revealed by Fourier transform-infrared (FT-IR) microspectroscopy. The presence of a casein kinase II-like activity in the mineralizing cultures, the ability of specific inhibitors of this enzyme to block mineralization, and the known ability of beta GP to block phosphoprotein phosphatase activity suggests that altered patterns of matrix protein phosphorylation may influence mineral deposition in these cultures.
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PMID:The mechanism of beta-glycerophosphate action in mineralizing chick limb-bud mesenchymal cell cultures. 891 77

Culture of mesangial cells (MCs) in 5.6 vs. 30.0 mmol/l glucose for 3 weeks induced a sustained increase in protein kinase C (PKC) activity, transforming growth factor (TGF)-beta1 mRNA, bioactive TGF-beta, and collagen synthesis. Nitric oxide (NO), generated exogenously by the NO donor S-nitroso-N-acetyl, D,L-penicillamine (SNAP) or endogenously after the exposure of MC to interleukin-1beta (IL-1beta), suppressed bioactive TGF-beta in MCs cultured in 5.6 or 30.0 mmol/l glucose and suppressed or abolished increases in TGF-beta1 mRNA and collagen synthesis induced by high concentrations of glucose or phorbol 12,13-dibutyrate without altering values obtained with normal glucose concentrations. SNAP had a transient suppressive effect on PKC activity, which may explain at least in part some of the actions of SNAP. The selective inhibitor of PKC, bisindolylmaleimide (GFX), mimicked NO action. The ability of SNAP and IL-1beta to suppress TGF-beta and collagen synthesis was not mediated by cGMP, since the cGMP analog, 8-Br-PET-cGMP, did not mimic NO action and an antagonist of cGMP-dependent protein kinase, Rp-8-pCPT-cGMPs, did not prevent the inhibitory actions of SNAP. N-omega-L-arginine methyl ester (NMMA) increased TGF-beta in glomerular capillary endothelial cells (GCECs) and stimulated collagen synthesis by MC in a co-culture with GCECs. Captopril inhibited TGF-beta and collagen synthesis and increased cGMP in co-cultures of GCECs and MCs. These effects of captopril were abolished by NMMA, implying mediation by NO. Thus, endogenous NO produced by GCECs may modulate TGF-beta production by both GCECs and MCs and act to suppress matrix protein synthesis by MCs.
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PMID:Nitric oxide inhibition of transforming growth factor-beta and collagen synthesis in mesangial cells. 907 10


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