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Casein Kinase (casein + kinase)
Terms modified by Casein Kinase Selected AbstractsCasein kinase 2 specifically binds to and phosphorylates the carboxy termini of ENaC subunitsFEBS JOURNAL, Issue 18 2002Haikun Shi A number of findings have suggested the involvement of protein phosphorylation in the regulation of the epithelial Na+ channel (ENaC). A recent study has demonstrated that the C tails of the , and , subunits of ENaC are subject to phosphorylation by at least three protein kinases [Shi, H., Asher, C., Chigaev, A., Yung, Y., Reuveny, E., Seger, R. & Garty, H. (2002) J. Biol. Chem. 277, 13539,13547]. One of them was identified as ERK which phosphorylates ,T613 and ,T623 and affects the channel interaction with Nedd4. The current study identifies a second protein kinase as casein kinase 2 (CK2), or CK-2-like kinase. It phosphorylates ,S631, a well-conserved serine on the , subunit. Such phosphorylation is observed both in vitro using glutathione-S-transferase,ENaC fusion proteins and in vivo in ENaC-expressing Xenopus oocytes. The , subunit is weakly phosphorylated by this protein kinase on another residue (,T599), and the C tail of , is not significantly phosphorylated by this kinase. Thus, CK2 may be involved in the regulation of the epithelial Na+ channel. [source] Structure of human protein kinase CK2,2 with a potent indazole-derivative inhibitorACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 2 2009Tetsuko Nakaniwa Casein kinase 2 (CK2) is a serine/threonine kinase that functions as a heterotetramer composed of two catalytic subunits (CK2,1 or CK2,2) and two regulatory subunits (CK2,). The two isozymes CK2,1 and CK2,2 play distinguishable roles in healthy subjects and in patients with diseases such as cancer, respectively. In order to develop novel CK2,1-selective inhibitors, the crystal structure of human CK2,2 (hCK2,2) complexed with a potent CK2, inhibitor which binds to the active site of hCK2,2 was determined and compared with that of human CK2,1. While the two isozymes exhibited a high similarity with regard to the active site, the largest structural difference between the isoforms occurred in the ,4,,5 loop responsible for the CK2,,CK2, interface. The top of the N-terminal segment interacted with the ,4,,5 loop via a hydrogen bond in hCK2,2 but not in hCK2,1. Thus, the CK2,,CK2, interface is a likely target candidate for the production of selective CK2,1 inhibitors. [source] Changes in the activities of protein phosphatase type 1 and type 2A in sea urchin embryos during early developmentDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 4 2000Manabu Kawamoto In the eggs and embryos of sea urchins, the activity of protein phosphatase type 2A (PP2A) increased during the developmental period between fertilization and the morula stage, decreased after the prehatching blastula stage and increased again after hatching. The PP2A activity changed keeping pace with alteration to the activities of cAMP-dependent protein kinase (A kinase), Ca2+/calmodulin-dependent protein kinase (CaM kinase) and casein kinase. Probably, PP2A contributes to the quick turning off of cellular signals because of protein phosphorylation. The activity of protein phosphatase type 1 (PP1) was not detectable up to the morula stage and appreciably increased thereafter. In the isolated nucleus fraction, specific activities of PP1 and PP2A were higher than in whole embryos at all stages in early development. Exponential increase in the number of nuclei because of egg cleavage probably makes PP1 activity detectable in whole embryos after the morula stage. In isolated nuclei, the activities of PP1 and PP2A appreciably decreased after hatching, whereas the activities of A kinase, Ca2+/phospholipid-dependent protein kinase (C kinase) and CaM kinase, as well as casein kinase, became higher. In nuclei, cellular signals caused by protein phosphorylation after hatching do not seem to be turned off by these protein kinases so quickly as before hatching. The PP1 and PP2A in nuclei also seem to contribute to the elimination of signal noise. [source] Regulation of ,FosB transcriptional activity by Ser27 phosphorylationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2007Paula G. Ulery Abstract The transcription factor, ,FosB, is an important mediator of the long-term plasticity induced in brain by chronic exposure to drugs of abuse, stress, or several other psychoactive stimuli. We have previously demonstrated that the casein kinase 2 (CK2)-mediated phosphorylation of a highly conserved N-terminal serine (Ser27) plays a critical role in regulating ,FosB's unusual stability, while it does not affect that of the full-length FosB protein. In the present study, we analysed whether CK2 and Ser27 phosphorylation also play a role in regulating ,FosB's transcriptional activity. Our findings indicate that CK2 activation increases ,FosB's transactivation potential, while CK2 inhibition decreases it. Further, we show that preventing Ser27 phosphorylation by mutating the site to Ala results in a significant decrease in ,FosB transactivation, without affecting ,FosB's subcellular localization or DNA-binding affinity. In contrast, Ser27 does not seem to play a role in the transactivation potential of full-length FosB. These findings constitute the first evidence of a role for phosphorylation in ,FosB's transcriptional activity. [source] Casein kinase 2 specifically binds to and phosphorylates the carboxy termini of ENaC subunitsFEBS JOURNAL, Issue 18 2002Haikun Shi A number of findings have suggested the involvement of protein phosphorylation in the regulation of the epithelial Na+ channel (ENaC). A recent study has demonstrated that the C tails of the , and , subunits of ENaC are subject to phosphorylation by at least three protein kinases [Shi, H., Asher, C., Chigaev, A., Yung, Y., Reuveny, E., Seger, R. & Garty, H. (2002) J. Biol. Chem. 277, 13539,13547]. One of them was identified as ERK which phosphorylates ,T613 and ,T623 and affects the channel interaction with Nedd4. The current study identifies a second protein kinase as casein kinase 2 (CK2), or CK-2-like kinase. It phosphorylates ,S631, a well-conserved serine on the , subunit. Such phosphorylation is observed both in vitro using glutathione-S-transferase,ENaC fusion proteins and in vivo in ENaC-expressing Xenopus oocytes. The , subunit is weakly phosphorylated by this protein kinase on another residue (,T599), and the C tail of , is not significantly phosphorylated by this kinase. Thus, CK2 may be involved in the regulation of the epithelial Na+ channel. [source] CK2,tes gene encodes a testis-specific isoform of the regulatory subunit of casein kinase 2 in Drosophila melanogasterFEBS JOURNAL, Issue 5 2002Alla I. Kalmykova An earlier described CK2,tes gene of Drosophila melanogaster is shown to encode a male germline specific isoform of regulatory ,,subunit of casein kinase 2. Western-analysis using anti-CK2,tes Ig revealed CK2,tes protein in Drosophila testes extract. Expression of a CK2,tes,,-galactosidase fusion protein driven by the CK2,tes promoter was found in transgenic flies at postmitotic stages of spermatogenesis. Examination of biochemical characteristics of a recombinant CK2,tes protein expressed in Escherichia coli revealed properties similar to those of CK2,: (a) CK2,tes protein stimulates CK2, catalytic activity toward synthetic peptide; (b) it inhibits phosphorylation of calmodulin and mediates stimulation of CK2, by polylysine; (c) it is able to form (CK2,tes)2 dimers, as well as (CK2,)2(CK2,tes)2 tetramers. Using the yeast two-hybrid system and coimmunoprecipitation analysis of protein extract from Drosophila testes, we demonstrated an association between CK2,tes and CK2,. Northern-analysis has shown that another regulatory (,,) subunit found recently in D. melanogaster genome is also testis-specific. Thus, we describe the first example of two tissue-specific regulatory subunits of CK2 which might serve to provide CK2 substrate recognition during spermatogenesis. [source] Trypanosoma brucei brucei induces alteration in the head proteome of the tsetse fly vector Glossina palpalis gambiensisINSECT MOLECULAR BIOLOGY, Issue 6 2007T. Lefèvre Abstract Parasitic manipulations of host behaviour are known from a wide range of host,parasite associations. However, the understanding of these phenomena is far from complete and detailed investigation of their proximate causes is needed. Many studies report behavioural modifications, such as altered feeding rates in tsetse fly (Glossina) infected with the mature transmissible stage (i.e. metacyclic) of the trypanosomes. Here, bidimensional (2D) gel electrophoresis and mass spectrometry were employed to analyse and compare the head proteome between four Glossina palpalis gambiensis categories (uninfected, refractory, mature infection, immature infection). Twenty-four protein spots specifically present or absent in the head of metacyclic-infected flies were observed. These protein spots were subsequently identified and functionally classified as glycolitic, neurotransmiter synthesis, signalling, molecular chaperone and transcriptional regulation proteins. Our results indicate altered energy metabolism in the head of metacyclic-infected tsetse flies. Some of the proteins identified, such as casein kinase 2 and jun kinase have previously been shown to play critical roles in apoptosis in insect neurones. In addition, we found two pyridoxal-dependent decarboxylases (dopa decarboxylase and alpha methyldopa hypersensitive protein), suggesting a modification of serotonin and/or dopamine in the brain of metacyclic-infected tsetse flies. Our data pave the way for future investigation of the alteration of the glossina central nervous system during infection by trypanosomes. [source] Basic region of residues 228,231 of protein kinase CK1, is involved in its interaction with axin: Binding to axin does not affect the kinase activity,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2005Pablo Sobrado Abstract Protein kinase CK1, also known as casein kinase 1, participates in the phosphorylation of ,-catenin, which regulates the functioning of the Wnt signaling cascade involved in embryogenesis and carcinogenesis. ,-catenin phosphorylation occurs in a multiprotein complex assembled on the scaffold protein axin. The interaction of CK1, from Danio rerio with mouse-axin has been studied using a pull-down assay that uses fragments of axin fused to glutathione S transferase, which is bound to glutathione sepharose beads. The results indicate that the three lysines present in the basic region of residues 228,231 of CK1, are necessary for the binding of CK1 to axin. Lysine 231 is particularly important in this interaction. In order to define the relevance of the axin-CK1, interaction, the effect of the presence of axin on the phosphorylating activity of CK1, was tested. It is also evident that the region of axin downstream of residues 503,562 is required for CK1, interaction. The binding of CK1, to axin fragment 292,681 does not facilitate the phosphorylation of ,-catenin despite the fact that this axin fragment can also bind ,-catenin. Binding of CK1, to axin is not required for the phosphorylation of axin itself and, likewise, axin does not affect the kinetic parameters of the CK1, towards casein or a specific peptide substrate. © 2004 Wiley-Liss, Inc. [source] Protective up-regulation of CK2 by mutant huntingtin in cells co-expressing NMDA receptorsJOURNAL OF NEUROCHEMISTRY, Issue 3 2008Mannie M. Y. Fan Abstract Huntington's disease is caused by a polyglutamine expansion in the huntingtin (htt) protein, and previous data indicate that over-activation of NMDA receptors (NMDARs) may be involved in the selective degeneration of cells expressing NR1/NR2B NMDARs. We used KinetworksÔ multi-immunoblotting screens to examine expression of 76 protein kinases, 18 protein phosphatases, 25 heat shock/stress proteins, and 27 apoptosis proteins in human embryonic kidney 293 cells transfected with NR1/NR2B and htt containing 15 (htt-15Q; wild-type) or 138 (htt-138Q; mutant) glutamine repeats. Follow-up experiments revealed several proteins involved in the heat-shock response pathway to be up-regulated in the soluble fraction from cells expressing htt-138Q, including protein phosphatase 5 and cyclin-dependent kinase 5. Increased expression in the soluble fraction of htt-138Q-expressing cells was also noted for the stress- and calcium-activated protein-serine/threonine kinase casein kinase 2, a change which was confirmed in striatal tissue of yeast artificial chromosome transgenic mice expressing full-length mutant htt. Inhibition of casein kinase 2 activity in cultured striatal neurons from these mice significantly exacerbated NMDAR-mediated toxicity, as assessed by labeling of apoptotic nuclei. Our findings are consistent with up-regulation of components of the stress response pathway in the presence of polyglutamine-expanded htt and NR1/NR2B which may reflect an attempt at the cellular level to ameliorate the detrimental effects of mutant htt expression. [source] Neuroprotective effects of Brazilian green propolis and its main constituents against oxygen-glucose deprivation Stress, with a gene-expression analysisPHYTOTHERAPY RESEARCH, Issue 10 2009Yoshimi Nakajima Abstract Our purpose was to investigate the neuroprotective effects (and the underlying mechanism) exerted by water extract of Brazilian green propolis (WEP) and its main constituents against the neuronal damage induced by oxygen-glucose deprivation (OGD)/reoxygenation in retinal ganglion cells (RGC-5, a rat ganglion cell-line transformed using E1A virus). Cell damage was induced by OGD 4 h plus reoxygenation 18 h exposure. In RGC-5, and also in PC12 (rat pheochromocytoma, neuronal cells), WEP and some of its main constituents attenuated the cell damage. At the end of the period of OGD/reoxygenation, RNA was extracted and DNA microarray analysis was performed to examine the gene-expression profile in RGC-5. Expression of casein kinase 2 (CK2) was down-regulated and that of Bcl-2-related ovarian killer protein (Bok) was up-regulated following OGD stress, results that were confirmed by quantitative reverse transcriptase-PCR (qRT-PCR). These effects were normalized by WEP. Our findings indicate that WEP has neuroprotective effects against OGD/reoxygenation-induced cell damage and that certain constituents of WEP (caffeoylquinic acid derivatives, artepillin C, and p -coumaric acid) may be partly responsible for its neuroprotective effects. Furthermore, the protective mechanism may involve normalization of the expressions of antioxidant- and apoptosis-related genes (such as CK2 and Bok, respectively). Copyright © 2009 John Wiley & Sons, Ltd. [source] | |||||||||||||