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The FEBS Journal

Cover image for Vol. 278 Issue 12

June 2011

Volume 278, Issue 12

Pages 1969–2179

  1. Minireview Series

    1. Top of page
    2. Minireview Series
    3. Minireview
    4. Original Articles
    5. Author Index
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      Tec family kinases (page 1969)

      Liang Yu and C. I. Edvard Smith

      Version of Record online: 18 MAY 2011 | DOI: 10.1111/j.1742-4658.2011.08135.x

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      Tec family kinases (TFKs) are ancient kinases, vital for the development of both mammals and fruit flies. The first TFKs were described 20 years ago, and one of them, BTK, was found to be vital for B-lymphocyte development. However, during the last five years several seminal discoveries have been made, significantly advancing our understanding of these signal transducers.

  2. Minireview

    1. Top of page
    2. Minireview Series
    3. Minireview
    4. Original Articles
    5. Author Index
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      Tec family kinases: Itk signaling and the development of NKT αβ and γδ T cells (pages 1970–1979)

      Qian Qi, Arun Kumar Kannan and Avery August

      Version of Record online: 29 MAR 2011 | DOI: 10.1111/j.1742-4658.2011.08074.x

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      Tec family tyrosine kinase interleukin-2 inducible T-cell kinase (Itk) is involved in the development and function of conventional αβ T cells. However, less is known about its role in non-conventional T cells. Here we discuss the role of Itk in the development of invariant NKT αβ cells, as well as a smaller population NKT-like γδ T cells.

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      Tec family kinases Itk and Rlk / Txk in T lymphocytes: cross-regulation of cytokine production and T-cell fates (pages 1980–1989)

      Julio Gomez-Rodriguez, Zachary J. Kraus and Pamela L. Schwartzberg

      Version of Record online: 29 MAR 2011 | DOI: 10.1111/j.1742-4658.2011.08072.x

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      Tec family kinases are critical modulators of T-cell receptor signaling and are important for the full activation of phospholipase C-γ, Ca2+ and Erk in both developing thymocytes and peripheral T cells. Through regulation of these signaling pathways, Tec kinases influence the development of distinct cytokine-producing innate-type T-cell populations in the thymus and peripheral T-cell populations.

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      Tec family kinases: regulation of FcεRI-mediated mast-cell activation (pages 1990–2000)

      Wilfried Ellmeier, Anastasia Abramova and Alexandra Schebesta

      Version of Record online: 29 MAR 2011 | DOI: 10.1111/j.1742-4658.2011.08073.x

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      Mast cells are key players in type I hypersensitivity reactions, however they also regulate normal physiological processes that link innate and adaptive immune responses. Members of the Tec family of protein tyrosine kinases are crucial regulators of mast cell activation. Here we review the current knowledge about the role of Tec family kinases in FcεRI-mediated signaling pathways in the mast cell.

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      TEC family kinases in health and disease – loss-of-function of BTK and ITK and the gain-of-function fusions ITK–SYK and BTK–SYK (pages 2001–2010)

      Alamdar Hussain, Liang Yu, Rani Faryal, Dara K. Mohammad, Abdalla J. Mohamed and C. I. Edvard Smith

      Version of Record online: 18 MAY 2011 | DOI: 10.1111/j.1742-4658.2011.08134.x

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      BTK and ITK are TEC-family kinases. In 1993 loss-of-function mutations in the BTK gene were reported as the cause of X-linked agammaglobulinemia (XLA) and in 2009 an inactivating mutation in the ITK gene was shown to cause susceptibility to lethal Epstein-Barr virus infection. Recently, a tumor-causing, gain-of-function fusion in ITK-SYK was described. Both ITK and BTK represent interesting targets for inhibition.

  3. Original Articles

    1. Top of page
    2. Minireview Series
    3. Minireview
    4. Original Articles
    5. Author Index
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      Heme binding to the second, lower-affinity site of the global iron regulator Irr from Rhizobium leguminosarum promotes oligomerization (pages 2011–2021)

      Gaye F. White, Chloe Singleton, Jonathan D. Todd, Myles R. Cheesman, Andrew W. B. Johnston and Nick E. Le Brun

      Version of Record online: 17 MAY 2011 | DOI: 10.1111/j.1742-4658.2011.08117.x

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      The iron responsive regulator Irr regulates genes in response to heme. In addition to a high affinity site located at a conserved His-Xxx-His (HxH) motif, Irr from Rhizobium leguminosarum also binds heme at a lower affinity second site. Here we show that the second site involves coordination by His46 and probably His66, and that heme-binding at this site promotes Irr oligomerisation.

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      Increased flexibility and liposome-binding capacity of CD1e at endosomal pH (pages 2022–2033)

      Natalia Bushmarina, Sylvie Tourne, Gaëlle Giacometti, François Signorino-Gelo, Luis F. Garcia-Alles, Jean-Pierre Cazenave, Daniel Hanau and Henri de la Salle

      Version of Record online: 13 MAY 2011 | DOI: 10.1111/j.1742-4658.2011.08118.x

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      In dendritic cells, when CD1e proteins reach the lysosomes, their N-terminal end is cleaved and they are cleaved into an active soluble form which facilitates the processing of complex lipid antigens. At lysosomal pH, they display properties which are expected to facilitate their function. In particular, they optimally interact with the surfaces of liposomes enriched in anionic lysosomal lipids.

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      Bacitracin inhibits the reductive activity of protein disulfide isomerase by disulfide bond formation with free cysteines in the substrate-binding domain (pages 2034–2043)

      Nina Dickerhof, Torsten Kleffmann, Ralph Jack and Sally McCormick

      Version of Record online: 17 MAY 2011 | DOI: 10.1111/j.1742-4658.2011.08119.x

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      Bacitracin is widely used as an inhibitor of protein disulfide isomerase (PDI). The mechanism of PDI inhibition by bacitracin is unknown. Here, we show by MALDI-TOF/TOF MS a direct interaction of bacitracin with PDI, which involves disulfide bond formation between an open thiol form of the bacitracin thiazoline ring and cysteines in the substrate binding domain of PDI.

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      MicroRNA-373, a new regulator of protein phosphatase 6, functions as an oncogene in hepatocellular carcinoma (pages 2044–2054)

      Nannan Wu, Xuyuan Liu, Xuemei Xu, Xingxing Fan, Min Liu, Xin Li, Qiping Zhong and Hua Tang

      Version of Record online: 17 MAY 2011 | DOI: 10.1111/j.1742-4658.2011.08120.x

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      MicroRNAs (miRNAs) are a class of small non-coding RNAs that function as key regulators of gene expression at the post-transcriptional level. In our research, we demonstrate that miR-373 can regulate cell cycle progression by targeting PPP6C transcripts and promotes the growth activity of hepatocellular carcinoma cells in vitro.

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      Auto-methylation of the mouse DNA-(cytosine C5)-methyltransferase Dnmt3a at its active site cysteine residue (pages 2055–2063)

      Abu Nasar Siddique, Renata Z. Jurkowska, Tomasz P. Jurkowski and Albert Jeltsch

      Version of Record online: 19 MAY 2011 | DOI: 10.1111/j.1742-4658.2011.08121.x

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      The mouse Dnmt3a DNA methyltransferase undergoes a slow automethylation reaction at its catalytic site cysteine residue which is stimulated in the presence of Dnmt3L and inhibited by substrate DNA. Automethylation leads to the inactivation of Dnmt3a and might contribute to enzyme regulation. The figure shows the active center of Dnmt3a with the catalytic cysteine and the coenzyme product S-adenosyl-homocysteine (orange).

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      Expression analysis of the nucleocytoplasmic lectin ‘Orysata’ from rice in Pichia pastoris (pages 2064–2079)

      Bassam Al Atalah, Elke Fouquaert, Dieter Vanderschaeghe, Paul Proost, Jan Balzarini, David F. Smith, Pierre Rougé, Yi Lasanajak, Nico Callewaert and Els J. M. Van Damme

      Version of Record online: 16 MAY 2011 | DOI: 10.1111/j.1742-4658.2011.08122.x

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      The Oryza sativa lectin (Orysata) is located in the nucleus and the cytoplasm of the plant cell. This lectin was expressed in the medium of the methylotrophic yeast Pichia pastoris and purified. Glycan array analysis revealed that Orysata interacts with high-mannose and more complex N-glycan structures. Orysata has potent anti-human immunodeficiency virus and anti-respiratory syncytial virus activity in cell culture.

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      Intrinsic local disorder and a network of charge–charge interactions are key to actinoporin membrane disruption and cytotoxicity (pages 2080–2089)

      Miguel A. Pardo-Cea, Inés Castrillo, Jorge Alegre-Cebollada, Álvaro Martínez-del-Pozo, José G. Gavilanes and Marta Bruix

      Version of Record online: 16 MAY 2011 | DOI: 10.1111/j.1742-4658.2011.08123.x

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      Actinoporins are a family of sea anemone proteins that bind to membranes and produce functional pores. In this work, the structural and dynamic NMR data on two disabled variants of Sticholysin II, R29Q and Y111N, support the importance of a network of electrostatic interactions anchored by R29, and the local disorder at Y111, for actinoporin membrane binding and lysis.

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      Energetic coupling along an allosteric communication channel drives the binding of Jun-Fos heterodimeric transcription factor to DNA (pages 2090–2104)

      Kenneth L. Seldeen, Brian J. Deegan, Vikas Bhat, David C. Mikles, Caleb B. McDonald and Amjad Farooq

      Version of Record online: 18 MAY 2011 | DOI: 10.1111/j.1742-4658.2011.08124.x

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      Isothermal titration calorimetry in conjunction with site-directed mutagenesis is employed here to map an intricate network of energetically-coupled basic residues driving the allosteric binding of Jun-Fos heterodimeric transcription factor to DNA. Surprisingly, many of the energetically-coupled residues are poorly conserved across other members of the bZIP family, underscoring the importance of basic residues in dictating the specificity of bZIP-DNA interactions.

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      Structural basis for substrate recognition by Erwinia chrysanthemi GH30 glucuronoxylanase (pages 2105–2116)

      Ľubica Urbániková, Mária Vršanská, Kristian B. R. Mørkeberg Krogh, Tine Hoff and Peter Biely

      Version of Record online: 23 MAY 2011 | DOI: 10.1111/j.1742-4658.2011.08127.x

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      The Erwinia chrysanthemi GH30 xylanase, specialized for glucuronoxylan hydrolysis, was crystallized with aldotetraouronic acid β-d-xylopyranosyl-(1[RIGHTWARDS ARROW]4)-[4-O-methyl-β-d-glucuronosyl-(1[RIGHTWARDS ARROW]2)]- β-d-xylopyranosyl-(1[RIGHTWARDS ARROW]4)-d-xylose as a ligand. The crystal structure of the enzyme-ligand complex was solved at 1.39 Å resolution. The ionic interaction of the enzyme guanidinium group of Arg293 with MeGlcA carboxylate appears to be indispensable for effective hydrolysis of the polysaccharide main chain.

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      Nautilin-63, a novel acidic glycoprotein from the shell nacre of Nautilus macromphalus (pages 2117–2130)

      Benjamin Marie, Isabelle Zanella-Cléon, Marion Corneillat, Michel Becchi, Gérard Alcaraz, Laurent Plasseraud, Gilles Luquet and Frédéric Marin

      Version of Record online: 17 MAY 2011 | DOI: 10.1111/j.1742-4658.2011.08129.x

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      To understand the molecular mechanism that controls the formation of the shell nacreous layer, we have investigated here the biochemistry of Nautilin-63, one of the main nacre matrix proteins of the cephalopod Nautilus macromphalus. In conclusion, Nautilin-63 exhibits ‘hybrid’ biochemical properties, found both in soluble and insoluble proteins, a fact that renders it difficult to classify according to the standard view on nacre proteins.

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      K182G substitution in DevR or C8G mutation in the Dev box impairs protein–DNA interaction and abrogates DevR-mediated gene induction in Mycobacterium tuberculosis (pages 2131–2139)

      Rajesh Kumar Gupta, Santosh Chauhan and Jaya Sivaswami Tyagi

      Version of Record online: 17 MAY 2011 | DOI: 10.1111/j.1742-4658.2011.08130.x

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      The present study aims to decipher the contribution of Lys182 in the function of DevR (DosR) dormancy regulator of Mycobacterium tuberculosis. DNase I footprinting and expression analyses demonstrate the importance of Lys182 interaction with G13 nucleotide in the binding motif for DevR function. Our findings provide valuable insights for designing molecules that interfere with DevR-mediated dormancy adaptation.

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      Identification of malic and soluble oxaloacetate decarboxylase enzymes in Enterococcus faecalis (pages 2140–2151)

      Martín Espariz, Guillermo Repizo, Víctor Blancato, Pablo Mortera, Sergio Alarcón and Christian Magni

      Version of Record online: 17 MAY 2011 | DOI: 10.1111/j.1742-4658.2011.08131.x

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      In the present study, we performed a biochemical characterization of two members of the malic enzyme family from Enterococcus faecalis. It was stated that MaeE is a malate oxidative decarboxylating enzyme whereas CitM is a soluble oxaloacetate decarboxylase. Our genetic studies showed that the citrate fermentation phenotype is not affected by citM deletion. Conversely, maeE gene disruption resulted in a malate deficient strain.

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      The chromosomal protein HMGN2 mediates lipopolysaccharide-induced expression of β-defensins in A549 cells (pages 2152–2166)

      Lu-Xia Deng, Gui-Xia Wu, Yue Cao, Bo Fan, Xiang Gao, Lin Luo and Ning Huang

      Version of Record online: 18 MAY 2011 | DOI: 10.1111/j.1742-4658.2011.08132.x

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      We verified that HMGN2 prolongs the retention time and enhances the accumulation of NF-κB p65 in the nucleus, and promotes the acetylation of p65 through increasing HAT’s activity and enhancing p65 Ser536 phosphorylation. Additionally, chromatin immunoprecipitation reveal that HMGN2 and p65 synergistically promote their specific binding to HBD-2 promoter, thereby affecting the downstream transcription of HBD-2 in A549 cells treated by lipopolysaccharide (LPS).

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      Metabolism of N-methyl-amide by cytochrome P450s : Formation and characterization of highly stable carbinol-amide intermediate (pages 2167–2178)

      Lionel Perrin, Nicolas Loiseau, François André and Marcel Delaforge

      Version of Record online: 19 MAY 2011 | DOI: 10.1111/j.1742-4658.2011.08133.x

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      Under mild acidic or neutral conditions, P450 metabolism of N-methylated substrates can lead to stable carbinol intermediate as shown by HPLC, MS and NMR analysis. Under stronger acidic conditions, their stability vanishes through deformylation. By considering the protocol usually used for extraction and analysis of this type of metabolite, carbinol-amide may thus be frequently ignored in drug metabolism pathway.

  4. Author Index

    1. Top of page
    2. Minireview Series
    3. Minireview
    4. Original Articles
    5. Author Index
    1. You have free access to this content
      Author index (page 2179)

      Version of Record online: 1 JUN 2011 | DOI: 10.1111/j.1742-4658.2011.07848.x

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