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Tao Zhou, Ning Li, Shikai Liu, Yulin Jin, Qiang Fu, Sen Gao, Yang Liu, Zhanjiang Liu
Adaptor proteins non-catalytic region of tyrosine kinase (NCK) and Abelson interactor (ABI) are crucial for disease response. NCK1 was identified to be a candidate gene for enteric septicemia of catfish (ESC) disease resistance, and was speculated to play similar roles during ESC and enteropathogenic Escherichia coli (EPEC) pathogenicity. ABI1 was reported as a positional candidate gene for bacterial cold water disease (BCWD) resistance in rainbow trout. In this study, three NCK genes and six ABI genes were identified in the channel catfish (Ictalurus punctatus) genome and blue catfish (I...
March 22, 2017: Developmental and Comparative Immunology
Philip J Law, Amit Sud, Jonathan S Mitchell, Marc Henrion, Giulia Orlando, Oleg Lenive, Peter Broderick, Helen E Speedy, David C Johnson, Martin Kaiser, Niels Weinhold, Rosie Cooke, Nicola J Sunter, Graham H Jackson, Geoffrey Summerfield, Robert J Harris, Andrew R Pettitt, David J Allsup, Jonathan Carmichael, James R Bailey, Guy Pratt, Thahira Rahman, Chris Pepper, Chris Fegan, Elke Pogge von Strandmann, Andreas Engert, Asta Försti, Bowang Chen, Miguel Inacio da Silva Filho, Hauke Thomsen, Per Hoffmann, Markus M Noethen, Lewin Eisele, Karl-Heinz Jöckel, James M Allan, Anthony J Swerdlow, Hartmut Goldschmidt, Daniel Catovsky, Gareth J Morgan, Kari Hemminki, Richard S Houlston
B-cell malignancies (BCM) originate from the same cell of origin, but at different maturation stages and have distinct clinical phenotypes. Although genetic risk variants for individual BCMs have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. We explored genome-wide association studies of chronic lymphocytic leukaemia (CLL, N = 1,842), Hodgkin lymphoma (HL, N = 1,465) and multiple myeloma (MM, N = 3,790). We identified a novel pleiotropic risk locus at 3q22...
January 23, 2017: Scientific Reports
Zhuomin Wu, Ping Wu, Xialin Zuo, Na Yu, Yixin Qin, Qian Xu, Shuai He, Bohong Cen, Wenjie Liao, Aimin Ji
In recent years, long noncoding RNAs (lncRNAs) have been shown to have critical roles in a broad range of cell biological processes. However, the activities of lncRNAs during ischemic stroke remain largely unknown. In this study, we carried out a genome-wide lncRNA microarray analysis in rat brains with ischemia/reperfusion (I/R) injury. The results revealed the differential expression of a subset of lncRNAs. Through the construction of lncRNA-mRNA co-expression networks, we identified lncRNA-N1LR as a novel I/R-induced lncRNA...
November 14, 2016: Molecular Neurobiology
Tao Zhou, Shikai Liu, Xin Geng, Yulin Jin, Chen Jiang, Lisui Bao, Jun Yao, Yu Zhang, Jiaren Zhang, Luyang Sun, Xiaozhu Wang, Ning Li, Suxu Tan, Zhanjiang Liu
Disease problems cause major economic losses for the aquaculture industries. In catfish, enteric septicemia of catfish (ESC), caused by the bacterial pathogen Edwardsiella ictaluri, is the leading disease problem, causing tens of millions of dollars of annual economic losses. In this study, we conducted a genome-wide association study to determine quantitative trait loci (QTL) for resistance against ESC using an interspecific hybrid system. Five hundred fish were used in the analysis and 192 phenotypic extremes were used for genotyping with the catfish 250K SNP arrays...
February 2017: Molecular Genetics and Genomics: MGG
Changyu Zhou, Jiayu Li, Jiarui Li, Yingchun Wan, Tao Li, Piyong Ma, Yingjian Wang, Haiyan Sang
The aim of the present study was to identify the differentially expressed microRNAs (DEMs) between Lynch syndrome (LS) and the normal colonic (N-C) control samples, predict the target genes (TGs) and analyze the potential functions of the DEMs and TGs. The miRNA expression dataset GSE30454, which included data of 13 LS and 20 N-C tissue samples, was downloaded from the Gene Expression Omnibus. The classical t-test in Linear Models for Microarray Data package was used for DEM identification. TG prediction was performed using 5 databases...
September 2016: Oncology Letters
Valentina Gandin, Laia Masvidal, Marie Cargnello, Laszlo Gyenis, Shannon McLaughlan, Yutian Cai, Clara Tenkerian, Masahiro Morita, Preetika Balanathan, Olivier Jean-Jean, Vuk Stambolic, Matthias Trost, Luc Furic, Louise Larose, Antonis E Koromilas, Katsura Asano, David Litchfield, Ola Larsson, Ivan Topisirovic
Ternary complex (TC) and eIF4F complex assembly are the two major rate-limiting steps in translation initiation regulated by eIF2α phosphorylation and the mTOR/4E-BP pathway, respectively. How TC and eIF4F assembly are coordinated, however, remains largely unknown. We show that mTOR suppresses translation of mRNAs activated under short-term stress wherein TC recycling is attenuated by eIF2α phosphorylation. During acute nutrient or growth factor stimulation, mTORC1 induces eIF2β phosphorylation and recruitment of NCK1 to eIF2, decreases eIF2α phosphorylation and bolsters TC recycling...
April 4, 2016: Nature Communications
Ava Keyvani Chahi, Claire E Martin, Nina Jones
Podocytes are key components of the kidney blood filtration barrier, and their ability to withstand hemodynamic strain is proposed to be closely tied to their unique and flexible cytoarchitecture. However, the mechanisms that control such mechanotransduction are poorly understood. We have previously established that tyrosine phosphorylation of the transmembrane protein nephrin promotes recruitment of the Nck1/2 cytoskeletal adaptor proteins and downstream actin remodeling. We now reveal that Nck integrates nephrin with the Hippo kinase cascade through association with the adaptor protein WTIP...
June 10, 2016: Journal of Biological Chemistry
Laura A New, Claire E Martin, Rizaldy P Scott, Mathew J Platt, Ava Keyvani Chahi, Colin D Stringer, Peihua Lu, Bozena Samborska, Vera Eremina, Tomoko Takano, Jeremy A Simpson, Susan E Quaggin, Nina Jones
Podocytes are specialized epithelial cells of the kidney blood filtration barrier that contribute to permselectivity via a series of interdigitating actin-rich foot processes. Positioned between adjacent projections is a unique cell junction known as the slit diaphragm, which is physically connected to the actin cytoskeleton via the transmembrane protein nephrin. Evidence indicates that tyrosine phosphorylation of the intracellular tail of nephrin initiates signaling events, including recruitment of cytoplasmic adaptor proteins Nck1 and Nck2 that regulate actin cytoskeletal dynamics...
August 2016: Journal of the American Society of Nephrology: JASN
Alexandre Dubrac, Gael Genet, Roxana Ola, Feng Zhang, Laurence Pibouin-Fragner, Jinah Han, Jiasheng Zhang, Jean-Léon Thomas, Alain Chedotal, Martin A Schwartz, Anne Eichmann
BACKGROUND: Sprouting angiogenesis is a key process driving blood vessel growth in ischemic tissues and an important drug target in a number of diseases, including wet macular degeneration and wound healing. Endothelial cells forming the sprout must develop front-rear polarity to allow sprout extension. The adaptor proteins Nck1 and 2 are known regulators of cytoskeletal dynamics and polarity, but their function in angiogenesis is poorly understood. Here, we show that the Nck adaptors are required for endothelial cell front-rear polarity and migration downstream of the angiogenic growth factors VEGF-A and Slit2...
January 26, 2016: Circulation
Smriti Aryal A C, Kentaro Miyai, Yayoi Izu, Tadayoshi Hayata, Takuya Notomi, Masaki Noda, Yoichi Ezura
Migration of the cells in osteoblastic lineage, including preosteoblasts and osteoblasts, has been postulated to influence bone formation. However, the molecular bases that link preosteoblastic/osteoblastic cell migration and bone formation are incompletely understood. Nck (noncatalytic region of tyrosine kinase; collectively referred to Nck1 and Nck2) is a member of the signaling adaptors that regulate cell migration and cytoskeletal structures, but its function in cells in the osteoblastic lineage is not known...
December 15, 2015: Proceedings of the National Academy of Sciences of the United States of America
Lama Yamani, Bing Li, Louise Larose
Increasing evidence strongly supports a critical role for PERK in regulating pancreatic β cell function. In agreement, we previously reported that enhancing PERK basal activity, by silencing the SH domain-containing adaptor protein Nck1 in pancreatic β cells, increased insulin content in a PERK-dependent manner. Here we report that Nck1-deficient MIN6 cells display normal overall morphology while as expected increased number of secretory granules. Furthermore, we demonstrate that cell survival to diabetes-relevant stresses is increased, while cell viability in response to chemical endoplasmic reticulum (ER) stress inducers is not changed...
December 2015: Cellular Signalling
Pussadee Paensuwan, Jatuporn Ngoenkam, Boonruang Khamsri, Kanlaya Preechanukul, Donruedee Sanguansermsri, Sutatip Pongcharoen
BACKGROUND: The engagement of the T cell receptor (TCR)-CD3 complex induces the formation of multiple signalling complexes, which are required for actin cytoskeletal rearrangement. The Wiskott-Aldrich syndrome protein (WASp) is a key regulator of actin polymerization that is recruited to the TCR activation site. Since WASp is a binding partner of adaptor protein Nck, which is recruited directly to the TCR CD3? subunit upon TCR ligation, therefore we proposed that the direct recruitment of Nck to TCR-CD3 may also bring WASp directly to TCR-CD3...
September 2015: Asian Pacific Journal of Allergy and Immunology
Ciaran Lane, Jiansong Qi, James P Fawcett
As our understanding of motor circuit function increases, our need to understand how circuits form to ensure proper function becomes increasingly important. Recently, deleted in colorectal cancer (DCC) has been shown to be important in the development of spinal circuits necessary for gait. Importantly, humans with mutation in DCC show mirror movement disorders pointing to the significance of DCC in the development of spinal circuits for coordinated movement. Although DCC binds a number of ligands, the intracellular signaling cascade leading to the aberrant spinal circuits remains unknown...
September 2015: Journal of Neurochemistry
Zhenke Liu, Shujia Dai, Jonathan Bones, Somak Ray, Sangwon Cha, Barry L Karger, Jingyi Jessica Li, Lee Wilson, Greg Hinckle, Anthony Rossomando
A goal in recombinant protein production using Chinese hamster ovary (CHO) cells is to achieve both high specific productivity and high cell density. Addition of glucose to the culture media is necessary to maintain both cell growth and viability. We varied the glucose concentration in the media from 5 to 16 g/L and found that although specific productivity of CHO-DG44 cells increased with the glucose level, the integrated viable cell density decreased. To examine the biological basis of these results, we conducted a discovery proteomic study of CHO-DG44 cells grown under batch conditions in normal (5 g/L) or high (15 g/L) glucose over 3, 6, and 9 days...
July 2015: Biotechnology Progress
Derek L Clouthier, Cameron N Harris, Richard A Harris, Claire E Martin, Mira C Puri, Nina Jones
Development of the cardiovascular system is critically dependent on the ability of endothelial cells (ECs) to reorganize their intracellular actin architecture to facilitate migration, adhesion, and morphogenesis. Nck family cytoskeletal adaptors function as key mediators of actin dynamics in numerous cell types, though their role in EC biology remains largely unexplored. Here, we demonstrate an essential requirement for Nck within ECs. Mouse embryos lacking endothelial Nck1/2 expression develop extensive angiogenic defects that result in lethality at about embryonic day 10...
May 2015: Molecular and Cellular Biology
Hui Li, Julie Dusseault, Louise Larose
BACKGROUND: Activation of the PI3K/Akt pathway mediates crucial cellular functions regulated by receptor tyrosine kinases, such as cell growth, proliferation, survival and metabolism. Previously, we reported that the whole-body knockout of the Src homology domain-containing adaptor protein Nck1 improves overall glucose homeostasis and insulin-induced activation of the PI3K/Akt pathway in liver of obese mice. The aim of the current study is to elucidate the mechanism by which Nck1 depletion regulates hepatic insulin signaling...
2014: Cell Communication and Signaling: CCS
Chandrama Mukherjee, Baskar Bakthavachalu, Daniel R Schoenberg
Cytoplasmic capping is catalyzed by a complex that contains capping enzyme (CE) and a kinase that converts RNA with a 5'-monophosphate end to a 5' diphosphate for subsequent addition of guanylic acid (GMP). We identify the proline-rich C-terminus as a new domain of CE that is required for its participation in cytoplasmic capping, and show the cytoplasmic capping complex assembles on Nck1, an adapter protein with functions in translation and tyrosine kinase signaling. Binding is specific to Nck1 and is independent of RNA...
August 2014: PLoS Biology
Maija Suvanto, Timo Jahnukainen, Marjo Kestilä, Hannu Jalanko
BACKGROUND: Podocyte foot process effacement is a uniform finding in kidneys with heavy proteinuria. Its molecular mechanisms, however, are unsolved. We analyzed the expression of podocyte proteins in two kidney disorders: Congenital nephrotic syndrome of the Finnish type (CNF) and minimal change nephrotic syndrome (MCNS). METHODS: Immunoperoxidase and immunofluorescence stainings were used to semiquantitatively analyze the expression of 13 and 4 podocyte proteins from different cellular compartments in CNF and MCNS, respectively...
June 2015: Clinical and Experimental Nephrology
Marcus Lettau, Stefanie Kliche, Dieter Kabelitz, Ottmar Janssen
Nck adapter proteins link receptor and receptor-associated tyrosine kinases with proteins implicated in the regulation of the actin cytoskeleton. Nck is involved in a multitude of receptor-initiated signaling pathways and its physiological role thus covers aspects of tissue development and homeostasis, malignant transformation/invasiveness of tumour cells and also immune cell function. In T cells, changes of cell polarity and morphology associated with cellular activation and effector function crucially rely on the T cell receptor-mediated recruitment and activation of different actin-regulatory proteins to orchestrate and drive cytoskeletal reorganization at the immunological synapse...
July 2014: Molecular Immunology
Jatuporn Ngoenkam, Pussadee Paensuwan, Kanlaya Preechanukul, Boonruang Khamsri, Ichaya Yiemwattana, Esmeralda Beck-García, Susana Minguet, Wolfgang W A Schamel, Sutatip Pongcharoen
BACKGROUND: Signalling by the T cell antigen receptor (TCR) results in the activation of T lymphocytes. Nck1 and Nck2 are two highly related adaptor proteins downstream of the TCR that each contains three SH3 and one SH2 domains. Their individual functions and the roles of their SH3 domains in human T cells remain mostly unknown. RESULTS: Using specific shRNA we down-regulated the expression of Nck1 or Nck2 to approximately 10% each in Jurkat T cells. We found that down-regulation of Nck1 impaired TCR-induced phosphorylation of the kinases Erk and MEK, activation of the AP-1 and NFAT transcription factors and subsequently, IL-2 and CD69 expression...
2014: Cell Communication and Signaling: CCS
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