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PKC Phosphorylation Sites (pkc + phosphorylation_site)
Selected AbstractsActivity-dependent subcellular localization of NAC1EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2005Laxman Korutla Abstract The expression of the transcriptional regulator NAC1 is increased in the nucleus accumbens of rats withdrawn from cocaine self-administration, and in vivo studies indicate that the up-regulation is a compensatory mechanism opposing the acute effects of cocaine. Both mammalian two-hybrid assay and punctate localization largely in the nucleus suggest NAC1 is a transcriptional regulator. However, in this report it is shown that in differentiated PC12 and Neuro2A cells, as well as in primary cortical neurons, NAC1 is diffusely expressed not only in the cell nucleus but also in cytoplasm. Blockade of spontaneous electrical activity by tetrodotoxin prevented the diffuse expression of NAC1, and depolarization with high potassium concentrations induced diffuse cellular localization in non-differentiating cells. The use of protein kinase C (PKC) inhibitors and activator, as well as the systematic mutation of potential PKC phosphorylation sites in NAC1, demonstrated that phosphorylation of residue S245 by PKC is a necessary event inducing diffuse NAC1 expression outside of the nucleus. These observations indicate a potential non-transcriptional role for NAC1 in the brain. [source] HTLV-1 infection in blood donors from the Western Brazilian Amazon region: Seroprevalence and molecular study of viral isolatesJOURNAL OF MEDICAL VIROLOGY, Issue 11 2008Aline Cristina Mota-Miranda Abstract To determine the seroprevalence of HTLV-1 in Brazil, and to review the virus molecular epidemiology in this Amazon population (Rio Branco-Acre), 219 blood donors were screened for HTLV-1. Only one case of infection (0.46% seroprevalence) was detected during July 2004 screening at the Acre Hospital Foundation (FUNDACRE). Neighbor-joining and Maximum Likelihood phylogenetic analyses of two (n,=,2) complete LTR region sequences were performed with the PAUP* software. Since the HTLV-1 envelope surface (gp46) and transmembrane (gp21) glycoproteins are important for virus fitness, three envelope glycoproteins sequences (n,=,3) were analyzed using the Prosite tool to determinate potential protein sites. Phylogenetic analysis demonstrated that the new isolate described in this study, and the unpublished LTR strain described in a previous report belong to the Transcontinental subgroup of the Cosmopolitan subtype, inside the Latin American cluster. A similar result was obtained when submitting, to the Automated Genotyping System, three LTR partial sequences from a previous study of the seroprevalence of HTLV-1 in the same Amazon population. In all analyzed env sequences, the potential protein site was found: two PKC phosphorylation sites at amino acid (aa) positions 310,312 and 342,344, one CK2 phosphorylation site at 194,197aa, three N -glycosylation sites at 222,225aa, 244,247aa and 272,275aa, and a single N -myristylation site at 327,338aa. In conclusion, potential protein sites described in HTLV-1 gp46 and gp21 confirm the presence of conserved sites in the HTLV-1 envelope proteins, likewise phylogenetic analysis suggests a possible recent introduction of the virus into North Brazil. J. Med. Virol. 80:1966,1971, 2008. © 2008 Wiley-Liss, Inc. [source] Expression of p27BBP/eIF6 is highly modulated during Xenopus laevis embryogenesisMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 4 2006Maria Carmela Vaccaro Abstract Protein p27BBP/eIF6 is necessary for ribosomal function of all cells. Previous data showed that from mammals to yeast p27BBP/eIF6 is involved in the biogenesis of ribosomal subunit 60S and its association with the 60S prevents premature 80S formation regulated by PKC signaling, indicating that phosphorylation of p27BBP/eIF6 is needed for translation to occur. While in vitro p27BBP/eIF6 is constitutively expressed, and it has a high level of expression in cycling cells, in vivo its expression varies according to tissues and appears regulated by factors up to now unknown. p27BBP/eIF6 has never been investigated in developing organisms where its upregulation can be correlated with tissue growth and differentiation. In this study we have sequenced p27BBP/eIF6 cDNA and studied its expression during development of Xenopus laevis, as the first step for studying its regulation. The amino acid sequence is highly conserved with two putative PKC phosphorylation sites in serine, one site being typical of Xenopus. At the end of gastrulation, the p27BBP/eIF6 riboprobe localizes in the neural plate and in the paraxial mesoderm. In particular, from stage 24, a clear-cut localization occurs in the perspective head. In embryos exposed to teratogens, the localization of p27BBP/eIF6 riboprobe varies according to the change of head size caused by the treatment. p27BBP/eIF6 expression is particularly evident in differentiating olfactory pits, the lens, otic vesicles, and in branchial arches. Features of particular interest are p27BBP/eIF6 high level of expression in the eye field, and in the mid-hindbrain-boundary, two regions with high proliferative activity. Altogether, data indicate that a modulated expression of p27BBP/eIF6 occurs in developing anlagens in addition to a basal level of expression, and may suggest a correlation between p27BBP/eIF6 and proliferative activity. Moreover, the X. laevis cDNA isolation and characterization offer new hints for further studies in relation to potential p27BBP/eIF6 phosphorylation. Mol. Reprod. Dev. © 2006 Wiley-Liss, Inc. [source] The antihistamine fexofenadine does not affect IKr currents in a case report of drug-induced cardiac arrhythmiaBRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2002Constanze R Scherer The human HERG gene encodes the cardiac repolarizing K+ current IKr and is genetically inactivated in inherited long QT syndrome 2 (LQTS2). The antihistamine terfenadine blocks HERG channels, and can cause QT prolongation and torsades de pointes, whereas its carboxylate fexofenadine lacks HERG blocking activity. In the present study the ability of fexofenadine to block the K897T HERG channel variant was investigated. The underlying single nucleotide polymorphism (SNP) A2960C was identified in a patient reported to develop fexofenadine-associated LQTS. K897T HERG channels produced wild-type-like currents in Xenopus oocytes. Even at a concentration of 100 ,M, fexofenadine did not inhibit wild-type or K897T HERG channels. Coexpression of wild-type and K897T HERG with the ß-subunit MiRP1, slightly changed current kinetics but did not change sensitivity to terfenadine and fexofenadine. Western blot analysis and immunostaining of transiently transfected COS-7 cells demonstrated that overall expression level, glycosylation pattern and subcellular localization of K897T HERG is indistinguishable from wild-type HERG protein, and not altered in the presence of 1 ,M fexofenadine. We provide the first functional characterization of the K897T HERG variant. We demonstrated that K897T HERG is similar to wild-type HERG, and is insensitive to fexofenadine. Although the polymorphism changes PKA and PKC phosphorylation sites, regulation of K897T HERG by these kinases is not altered. Our results strongly indicate that QT lengthening and cardiac arrhythmia in the reported case of drug-induced LQT are not due to the K897T exchange or to an inhibitory effect of fexofenadine on cardiac IKr currents. British Journal of Pharmacology (2002) 137, 892,900. doi:10.1038/sj.bjp.0704873 [source] | ||||||||||