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)

Nopp140 is a nucleolar phosphoprotein of 140 kd that we originally identified and purified as a nuclear localization signal (NLS)-binding protein. Molecular characterization revealed a 10-fold repeated motif of highly conserved acidic serine clusters that contain an abundance of phosphorylation consensus sites for casein kinase II (CK II). Indeed, Nopp140 is one of the most phosphorylated proteins in the cell, and NLS binding was dependent on phosphorylation. Nopp140 was shown to shuttle between the nucleolus and the cytoplasm. Shuttling is likely to proceed on tracks that were revealed by immunoelectron microscopy. These tracks extend from the dense fibrillar component of the nucleolus across the nucleoplasm to some nuclear pore complexes. We suggest that Nopp140 functions as a chaperone for import into and/or export from the nucleolus.
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PMID:Nopp140 shuttles on tracks between nucleolus and cytoplasm. 162 16

A major phosphopeptide labeled in vivo, was identified in nucleolar protein B23 (Mr/pI = 37,000/5.1) after tryptic digestion. This peptide was purified by high performance liquid chromatography using reverse-phase (C8 and C18) columns. The phosphopeptide contains 20 amino acids including 1 phosphoserine, 7 glutamic acids, and 4 aspartic acids. The amino acid sequence is: His-Leu-Val-Ala-Val-Glu-Glu-Asp-Ala-Glu-Ser(P)-Glu-Asp-Glu-Asp- Glu-Glu-Asp-Val-Lys. This amino acid sequence is similar to that of nucleolar phosphoprotein C23 (8 consecutive amino acids were identical), and to the regulatory subunit (RII) of cAMP-dependent protein kinase (7 consecutive amino acids were identical, which is phosphorylated by casein kinase II (Carmichael, D.F., Geahlen, R.L., Allen, S.M., and Krebs, E.G. (1982) J. Biol. Chem 257, 10440-10445). The regions near these phosphorylation sites are enriched with glutamic and aspartic acids, suggesting that this acidic amino acid cluster may be essential for kinase recognition.
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PMID:Amino acid sequence of protein B23 phosphorylation site. 394 16

The monoclonal antibody G1C7, recognises both Xenopus nucleolin and a protein of 180 kDa present in Xenopus oocyte nucleoli. This antibody was used to obtain a cDNA clone encoding the 180 kDa protein now called xNopp180 (Xenopus nucleolar phosphoprotein of 180 kDa). Analysis of the deduced amino acid sequence from this cDNA shows that xNopp180 is almost entirely composed of alternating acidic and basic domains. We show that xNopp180 is heavily phosphorylated and that it contains multiple consensus sites for phosphorylation by casein kinase II and cdc2 kinase. In addition we show that xNopp180 is the 180 kDa antigen recognised by the monoclonal antibody No-114, thus allowing reinterpretation of previous work with this antibody. xNopp180 appears to be the Xenopus homolog of the rat nucleolar protein Nopp140. Nopp140 is a nuclear localisation signal binding protein that shuttles on curvilinear tracks between the nucleolus and the cytoplasm. Possible roles for xNopp180/Nopp140 in ribosome biogenesis are discussed.
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PMID:Identification and cDNA cloning of a Xenopus nucleolar phosphoprotein, xNopp180, that is the homolog of the rat nucleolar protein Nopp140. 759 94

We identified a novel human nucleolar phosphoprotein p130 (130 kDa) using a strategy for selecting monoclonal antibodies against nuclear proteins which oscillate in the cell cycle. p130 is localized in interphase nucleoli in a dotted manner. Complete extraction of p130 required a high concentration of salt (0.5 M NaCl) indicating that it binds firmly to the nucleolar components via ionic interaction. p130 is heavily phosphorylated, since alkaline phosphatase treatment converted the purified p130 into a 95 kDa product; this was further supported by the in vitro demonstration that cellular phosphatase and casein kinase II activities were responsible for the interchange of these two forms. Extracts of mitotic cells had lower concentrations of p130 compared to those of interphase cells suggesting that a proportion of p130 might be degraded during mitosis. Moreover, all the remaining p130 in mitotic cells was further phosphorylated, likely by a cdc2 kinase, resulting in increase in its solubility, and its dispersion throughout the entire cytoplasm. Thus, p130 in metaphase and anaphase cells was unable to be detected by immunofluorescence microscopy. At telophase, p130 reappeared and aggregated into a granular structure, resembling the prenucleolar bodies. These granules migrated from the nucleoplasm to the nucleoli in early G1-phase. Actinomycin D was able to induce segregation of p130-containing granules into the nucleoplasm, similar to the well-known behavior of the fibrillarin-containing granules, indicating that p130 is localized in the dense fibrillar component, a subnucleolar region for pre-rRNA synthesis and processing. The cDNA sequence of p130 revealed a remarkable feature, that a serine-rich stretch interspersed with acidic residues is repeated ten times. Such a characteristic is shared with a rat nucleolar phosphoprotein Nopp140, which is thought to shuttle between the nucleolus and the cytoplasm. Although p130 shows 74% identity to Nopp140, our observations suggest that during mitosis the functions of p130 are related to nucleologenesis.
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PMID:Cell-cycle-dependent alterations of a highly phosphorylated nucleolar protein p130 are associated with nucleologenesis. 765 14

Nucleolin is an abundant nucleolar phosphoprotein which has been implicated as a factor in various stages of ribosome synthesis, including transcription. Since androgens exert a profound effect on the rRNA synthesis in the target organ prostate, we have examined the nature of androgenic regulation of the amount and phosphorylation of nucleolin in this tissue. Phosphorylation of prostatic nucleolin is catalyzed in part by heparin-sensitive casein kinase 2 (CK-2) and by another (heparin-insensitive) protein kinase. Both the amount and phosphorylation of prostatic nucleolin are profoundly sensitive to androgens. Rapid reduction in the level and phosphorylation of nucleolin occurs following androgen deprivation, which corresponds to the ensuing cessation of prostatic growth leading to involution. Further, the loss of nucleolin phosphorylation and its degradation appear to be concordant. Administration of a single injection of 5 alpha-dihydrotestosterone to castrated animals causes an early increase in the amount and phosphorylation of nucleolin, starting in the prereplicative phase in the prostatic cell nucleus. These data suggest that early androgenic regulation of nucleolin expression and phosphorylation may play a role in nucleolar control mechanisms relevant to prostatic cell growth.
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PMID:Androgenic regulation of phosphorylation and stability of nucleolar protein nucleolin in rat ventral prostate. 830 45

Rat Nopp140, a nonribosomal protein of the nucleolus and coiled bodies, was characterized as one of the most highly phosphorylated proteins in the cell. Based on its subcellular location, its nuclear localization signal binding capacity, and its shuttling between the nucleolus and the cytoplasm, Nopp140 was proposed to function as a chaperone in ribosome biogenesis. This study shows that casein kinase II phosphorylates Nopp140 to its unusual high degree and identifies the yeast SRP40 gene product as immunologically and structurally related to rat Nopp140. SRP40 encodes an acidic (pI = 3. 9), serine-rich (49%) protein of 41 kDa whose carboxyl terminus exhibits 59% sequence identity to that of Nopp140. SRP40 localizes to the yeast nucleolus and is required at a specific cellular concentration for optimal growth as indicated by the negative effect on cell growth of both overexpression and deletion of its gene. Like Nopp140, SRP40 is phosphorylated by casein kinase II, but to a much lesser extent. While the parallels between these two proteins suggest that SRP40 is the bona fide yeast Nopp140 homolog, their disparities reflect the differences in nucleolar dynamics and regulation of ribosome biogenesis between yeast and vertebrates.
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PMID:Comparison of the rat nucleolar protein nopp140 with its yeast homolog SRP40. Differential phosphorylation in vertebrates and yeast. 870 24

Nucleophosmin (NPM) is an estrogen-regulated nucleolar phosphoprotein; a substrate for phosphorylation by p34cdc2 kinase, protein kinase C, and casein kinase II; and a repressor of the transcriptional regulating activities of the YY1 and IFN regulatory factor-1 transcription factors. We have completed a pilot study to determine whether autoantibodies to NPM are present in breast cancer patients and explored the ability of these autoantibodies to predict recurrence in breast cancer patients. One hundred breast cancer patients were studied: 50 who recurred, and 50 matched for age and length of follow-up but who did not recur. Patients' sera were collected at the times of diagnosis (T1), six months before recurrence (T2), and at recurrence (T3). Recurrent and nonrecurrent patients did not differ in autoantibody levels at the times of diagnosis or recurrence. However, antiNPM autoantibody levels increase significantly between diagnosis and six months before recurrence in recurrent patients, whereas no change occurs over the comparable time period in nonrecurrent patients (repeated measures ANOVA; P = 0.041). At recurrence, the levels return to those seen at diagnosis. The greater the change in levels between T1 and T2, the greater the risk of recurrence within the next 6 months (conditional logistic regression: increase in risk for highest versus lowest tertile of change from T1 to T2; odds ratio, 3.25; 95% confidence interval, 1.04-10.18; P = 0.043). Consistent with the estrogenic/antiestrogenic regulation of the antigen in breast cancer cells, the levels of antiNPM autoantibodies are decreased 6 months before recurrence in patients treated with the antiestrogen tamoxifen (P = 0.012). The association between antiNPM levels and recurrence remained after adjustment for confounding factors. Further study of antiNPM autoantibody levels as a new and simple, intermediate serum biomarker for predicting both the timing of recurrence and monitoring response to endocrine manipulations in breast cancer patients is warranted.
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PMID:Autoantibodies to the nuclear phosphoprotein nucleophosmin in breast cancer patients. 986 29

Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development caused by mutations in the gene TCOF1. Its gene product, treacle, consists mainly of a central repeat domain, which shows it to be structurally related to the nucleolar phosphoprotein Nopp140. Treacle remains mostly uncharacterized to date. Herein we show that it, like Nopp140, is a highly phosphorylated nucleolar protein. However, treacle fails to colocalize with Nopp140 to Cajal (coiled) bodies. As in the case of Nopp140, casein kinase 2 appears to be responsible for the unusually high degree of phosphorylation as evidenced by its coimmunoprecipitation with treacle. Based on these and other observations, treacle and Nopp140 exhibit distinct but overlapping functions. The majority of TCOF1 mutations in TCS lead to premature termination codons that could affect the cellular levels of the full-length treacle. We demonstrate however, that the cellular amount of treacle varies less than twofold among a collection of primary fibroblasts and lymphoblasts and regardless of whether the cells were derived from TCS patients or healthy individuals. Therefore, cells of TCS patients possess a mechanism to maintain wild-type levels of full-length treacle from a single allele.
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PMID:Characterization of the nucleolar gene product, treacle, in Treacher Collins syndrome. 1098

A variety of cell membrane proteins become phosphorylated in their ecto-domains by cell-surface protein kinase (ecto-PK) activities, as detected in a broad spectrum of cell types. This study reports the isolation and identification of a frequent ecto-PK substrate, ecto-p120, using HeLa cells as a model. Data from MS and further biochemical and immunochemical means identified ecto-p120 as a cell-surface homologue of human nucleolar phosphoprotein p140 (hNopp140), which belongs to the family of argyrophilic (AgNOR-stainable) proteins. The superposition of (32)P-labelled ecto-nucleolar phosphoprotein p140 (ecto-Nopp140) with anti-Nopp140 immunostaining could be demonstrated in a wide range of cell lines without any exceptions, suggesting a nearly universal occurrence of cell-surface Nopp140. A previous, tentative association of ecto-p120 with the nucleoplasmic pre-mRNA-binding protein hnRNP U has thus been supplanted, since improved purification techniques have allowed unambiguous identification of this ecto-PK cell-surface substrate. Furthermore, we have shown that rapid suppression of ecto-hNopp140 phosphorylation resulted upon a rise in the free extracellular calcium, while lowering the calcium concentrations returned ecto-Nopp140 phosphorylation to the original level. It is important to note that these Ca(2+)-dependent effects on ecto-Nopp140 phosphorylation are not accompanied by alterations in the phosphorylation of other ecto-PK substrates. Our results indicate that, in addition to nucleolin, a further nucleolar protein, which was considered initially to be strictly intracellular, is identified as a cell-surface phosphoprotein.
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PMID:Ecto-protein kinase substrate p120 revealed as the cell-surface-expressed nucleolar phosphoprotein Nopp140: a candidate protein for extracellular Ca2+-sensing. 1173 47

We have demonstrated previously that Nopp44/46, an abundant nucleolar phosphoprotein of Trypanosoma brucei, is associated with a protein kinase. In many organisms multiple nucleolar proteins are phosphorylated by the protein kinase CK2, formerly known as casein kinase II. Here we report the identification of two T. brucei genes, CK2a1and CK2a2, which encode protein kinases bearing signature motifs common to CK2 catalytic subunits. The protein specified by CK2a1, designated CK2alpha, was capable of associating with Nopp44/46 as assessed by yeast two-hybrid analysis. An epitope-tagged version of CK2alpha expressed in T. brucei colocalized with Nopp44/46, with a largely nucleolar localization. This localization contrasts with the predominantly nuclear localization of mammalian CK2. When expressed in Escherichia coli, TbCK2alpha was catalytically active and phosphorylated Nopp44/46. Together these data demonstrate that TbCK2alpha is a Nopp44/46-associated kinase. Competition assays revealed that, unlike most CK2s, TbCK2alpha discriminates highly between ATP and GTP. This distinction may be associated with the substitution of glutamic acid and alanine for the di-asparagine motif thought to participate in purine interaction.
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PMID:Molecular cloning of Trypanosoma brucei CK2 catalytic subunits: the alpha isoform is nucleolar and phosphorylates the nucleolar protein Nopp44/46. 1175 90


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