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Shp1 OR Shp2

Katrin Ehlers, Amey S Bhide, Dawit G Tekleyohans, Benjamin Wittkop, Rod J Snowdon, Annette Becker
Seed formation is a pivotal process in plant reproduction and dispersal. It begins with megagametophyte development in the ovule, followed by fertilization and subsequently coordinated development of embryo, endosperm, and maternal seed coat. Two closely related MADS-box genes, SHATTERPROOF 1 and 2 (SHP1 and SHP2) are involved in specifying ovule integument identity in Arabidopsis thaliana. The MADS box gene ARABIDOPSIS BSISTER (ABS or TT16) is required, together with SEEDSTICK (STK) for the formation of endothelium, part of the seed coat and innermost tissue layer formed by the maternal plant...
2016: PloS One
Elizabeth E Hjort, Weiqi Huang, Liping Hu, Elizabeth A Eklund
Icsbp/Irf8 is an interferon regulatory transcription factor that functions as a suppressor of myeloid leukemias. Consistent with this activity, Icsbp represses a set of genes encoding proteins that promote cell proliferation/survival. One such gene encodes Gas2, a calpain inhibitor. We previously found that increased Gas2-expression in Bcr-abl+ cells stabilized βcatenin; a Calpain substrate. This was of interest, because βcatenin contributes to disease progression in chronic myeloid leukemia (CML). Calpain has additional substrates implicated in leukemogenesis, including Stat5...
October 19, 2016: Oncotarget
V A Doss, Dharaniyambigai Kuberapandian
BACKGROUND: The objective of this study is to develop a new animal model based on signaling pathways to understand the pathophysiology, therapy of depression, and to investigate the antidepressant activity of Enicostemma littorale which is not yet established. METHODS: Animal models of depression were raised by physical methods and administration of methyl isobutyl ketone (100 mg/kg b.w., i.p.,) and a protein tyrosine phosphatase inhibitor, sodium orthovanadate (30 mg/kg b...
2016: International Journal of Preventive Medicine
Motasem Melhem, Mohamed Abu-Farha, Dinu Antony, Ashraf Al Madhoun, Chiara Bacchelli, Fadi Alkayal, Irina AlKhairi, Sumi John, Mohamad Alomari, Phillip L Beales, Osama Alsmadi
OBJECTIVE: To characterize the underlying genetic and molecular defects in a consanguineous family with life-long blood disorder manifested with thrombocytopenia (low platelets count) and anemia. METHODS: Genetic linkage analysis, exome sequencing and functional genomics were carried out to identify and characterize the defective gene. RESULTS: We identification of a novel truncation mutation (p.C108*) in Chromosome 6 Open Reading Frame 25 (C6orf25) gene in this family...
October 15, 2016: European Journal of Haematology
Salvador Iborra, María Martínez-López, Francisco J Cueto, Ruth Conde-Garrosa, Carlos Del Fresno, Helena M Izquierdo, Clare L Abram, Daiki Mori, Yolanda Campos-Martín, Rosa María Reguera, Benjamin Kemp, Sho Yamasaki, Matthew J Robinson, Manuel Soto, Clifford A Lowell, David Sancho
C-type lectin receptors sense a diversity of endogenous and exogenous ligands that may trigger differential responses. Here, we have found that human and mouse Mincle bind to a ligand released by Leishmania, a eukaryote parasite that evades an effective immune response. Mincle-deficient mice had milder dermal pathology and a tenth of the parasite burden compared to wild-type mice after Leishmania major intradermal ear infection. Mincle deficiency enhanced adaptive immunity against the parasite, correlating with increased activation, migration, and priming by Mincle-deficient dendritic cells (DCs)...
October 5, 2016: Immunity
Argyrios Tzouvelekis, Guoying Yu, Christian Lacks Lino Cardenas, Jose D Herazo-Maya, Rong Wang, Tony Woolard, Yi Zhang, Koji Sakamoto, Hojin Lee, Jae-Sung Yi, Giuseppe DeIuliis, Nikolaos Xylourgidis, Farida Ahangari, Patty J Lee, Vassilis Aidinis, Erica L Herzog, Robert Homer, Anton M Bennett, Naftali Kaminski
RATIONALE: Idiopathic Pulmonary Fibrosis (IPF) is a chronic fatal lung disease with dismal prognosis and no cure. The potential role of the ubiquitously expressed SH2 domain-containing-tyrosine phosphatase (SHP2) as a therapeutic target has not been studied in IPF Objectives: To determine the expression, mechanistic role and potential therapeutic utility of SHP2 in Pulmonary Fibrosis Methods: The effects of SHP2 overexpression and inhibition on fibroblast response to pro-fibrotic stimuli were analyzed in-vitro in primary human and mouse lung fibroblasts...
October 13, 2016: American Journal of Respiratory and Critical Care Medicine
Adam J de Smith, Juhi Ojha, Stephen S Francis, Erica Sanders, Alyson A Endicott, Helen M Hansen, Ivan Smirnov, Amanda M Termuhlen, Kyle M Walsh, Catherine Metayer, Joseph L Wiemels
High hyperdiploidy (HD), the most common cytogenetic subtype of B-cell acute lymphoblastic leukemia (B-ALL), is largely curable but significant treatment-related morbidity warrants investigating the biology and identifying novel drug targets. Targeted deep-sequencing of 538 cancer-relevant genes was performed in 57 HD-ALL patients lacking overt KRAS and NRAS hotspot mutations and lacking common B-ALL deletions to enrich for discovery of novel driver genes. One-third of patients harbored damaging mutations in epigenetic regulatory genes, including the putative novel driver DOT1L (n=4)...
September 24, 2016: Oncotarget
Kenta Maruyama, Takahiko Kawasaki, Masahide Hamaguchi, Motomu Hashimoto, Moritoshi Furu, Hiromu Ito, Takao Fujii, Naoki Takemura, Thangaraj Karuppuchamy, Takeshi Kondo, Takumi Kawasaki, Masahiro Fukasaka, Takuma Misawa, Tatsuya Saitoh, Yutaka Suzuki, Mikaël M Martino, Yutaro Kumagai, Shizuo Akira
Netrin 1 was initially identified as an axon guidance factor and recent reports indicate that it inhibits chemokine-directed monocyte migration. Despite its importance as a neuroimmune guidance cue, the role of netrin 1 in osteoclasts is largely unknown. Here we detected high netrin 1 levels in the synovial fluid of rheumatoid arthritis patients. Netrin 1 is potently expressed in osteoblasts and synovial fibroblasts, and IL17 robustly enhances netrin 1 expression in these cells. The binding of netrin 1 to its receptor UNC5b on osteoclasts resulted in activation of SHP1, which inhibited VAV3 phosphorylation and RAC1 activation...
September 28, 2016: Journal of Biological Chemistry
Antoine Buetti-Dinh, Thomas O'Hare, Ran Friedman
A large subset of anaplastic large cell lymphoma (ALCL) patients harbour a somatic aberration in which anaplastic lymphoma kinase (ALK) is fused to nucleophosmin (NPM) resulting in a constitutively active signalling fusion protein, NPM-ALK. We computationally simulated the signalling network which mediates pathological cell survival and proliferation through NPM-ALK to identify therapeutically targetable nodes through which it may be possible to regain control of the tumourigenic process. The simulations reveal the predominant role of the VAV1-CDC42 (cell division control protein 42) pathway in NPM-ALK-driven cellular proliferation and of the Ras / mitogen-activated ERK kinase (MEK) / extracellular signal-regulated kinase (ERK) cascade in controlling cell survival...
2016: PloS One
Beatrice Conti, Cristiana Porcu, Carmela Viscomi, Antonella Minutolo, Susan Costantini, Marco Corazzari, Gino Iannucci, Barbara Barbaro, Clara Balsano
HCV life cycle is strictly correlated with the hepatocyte lipid metabolism; moreover, the progression of HCV chronic hepatitis is accelerated by the presence of liver steatosis. Among the steatogenic genes deregulated during the HCV infection one of the most attractive is the Small Heterodimer Protein 1 (SHP1; NR0B2), that is involved in a remarkable number of metabolic functions. HCV NS5A is an essential and integral component of the HCV membranous-web replicon complex (RC) and plays an essential role to transfer the viral genome from the RCs to the surface of the lipid droplets (LDs) that, in turn, play a key function during HCV life cycle...
September 20, 2016: Oncotarget
Ippei Kikuchi, Atsushi Takahashi-Kanemitsu, Natsuki Sakiyama, Chao Tang, Pei-Jung Tang, Saori Noda, Kazuki Nakao, Hidetoshi Kassai, Toshiro Sato, Atsu Aiba, Masanori Hatakeyama
Evolutionally conserved Wnt, Hedgehog (Hh) and Notch morphogen pathways play essential roles in the development, homeostasis and pathogenesis of multicellular organisms. Nevertheless, mechanisms that intracellularly coordinate these signal inputs remain poorly understood. Here we found that parafibromin, a component of the PAF complex, competitively interacts with β-catenin and Gli1, thereby potentiating transactivation of Wnt- and Hh-target genes in a mutually exclusive manner. Parafibromin also binds to the Notch intracellular domain (NICD), enabling concerted activation of Wnt- and Notch-target genes...
September 21, 2016: Nature Communications
Ruo-Yu Zhang, Zhi-Hong Yu, Lifan Zeng, Sheng Zhang, Yunpeng Bai, Jinmin Miao, Lan Chen, Jingwu Xie, Zhong-Yin Zhang
Melanoma ranks among the most aggressive and deadly human cancers. Although a number of targeted therapies are available, they are effective only in a subset of patients and the emergence of drug resistance often reduces durable responses. Thus there is an urgent need to identify new therapeutic targets and develop more potent pharmacological agents for melanoma treatment. Herein we report that SHP2 levels are frequently elevated in melanoma, and high SHP2 expression is significantly associated with more metastatic phenotype and poorer prognosis...
September 16, 2016: Oncotarget
Prakasit Rattanatanyong, Somboon Keelawat, Nakarin Kitkumthorn, Apiwat Mutirangura
BACKGROUND: Methylation of promoter 2 of the SHP1 gene is epithelial cell specific, with reported potential as a lymph node metastatic marker. OBJECTIVE: To demonstrate SHP1-P2 methylation-specific quantitative PCR effectiveness in detecting colorectal cancer (CRC) DNA in lymph nodes. MATERIALS AND METHODS: SHP1-P2 methylation levels were measured in lymph nodes of CRC patients and compared with pathological findings and patient prognosis...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
Mohammad Diab, Alon Vitenshtein, Yaron Drori, Rachel Yamin, Oded Danziger, Rachel Zamostiano, Michal Mandelboim, Eran Bacharach, Ofer Mandelboim
The innate sensing system is equipped with PRRs specialized in recognizing molecular structures (PAMPs) of various pathogens. This leads to the induction of anti-viral genes and inhibition of virus growth. Human Metapneumovirus (HMPV) is a major respiratory virus that causes an upper and lower respiratory tract infection in children. In this study we show that upon HMPV infection, the innate sensing system detects the viral RNA through the RIG-I sensor leading to induction of CEACAM1 expression. We further show that CEACAM1 is induced via binding of IRF3 to the CEACAM1 promoter...
September 12, 2016: Oncotarget
Yi-Jen Liao, Yen-Hua Lee, Fu-Ling Chang, Hsun Ho, Chin-Han Huang, Yuh-Ching Twu
BACKGROUND: Phosphorylation status of the transcription factor CCAAT/enhancer binding protein α (C/EBPα) has been demonstrated in a human hematopoietic cell model to regulate the formation of branched I antigen by affecting its binding affinity to the promoter region of the IGnTC gene during erythroid and granulocytic differentiation. STUDY DESIGN AND METHODS: The K-562 cell line was induced to differentiate into red blood cells (RBCs) or granulocytes by sodium butyrate or retinoic acid, respectively, to study the involvement of three MAP kinase pathways in I antigen synthesis...
September 7, 2016: Transfusion
Nicholas R J Gascoigne, Joanna Brzostek, Monika Mehta, Oreste Acuto
Thymocyte development and maintenance of peripheral T-cell numbers and functions are critically dependent on T-cell receptor (TCR) signal strength. SHP1 (Src homology region 2 domain-containing phosphatase-1), a tyrosine phosphatase, acts as a negative regulator of TCR signal strength. Moreover, germline SHP1 knockout mice have shown impaired thymic development. However, this has been recently questioned by an analysis of SHP1 conditional knockout mice, which reported normal thymic development of SHP1 deficient thymocytes...
September 2016: European Journal of Immunology
Alexander Dee, Kairong Li, Xin Heng, Qiuxia Guo, James Y H Li
During embryogenesis, the tectum (dorsal midbrain) displays gradients in both gene expression and cytogenesis along the anteroposterior axis, and eventually produces the superior colliculus anteriorly and inferior colliculus posteriorly. Although it is known that different strengths and durations of FGF signaling control the developmental gradient and cell fate decision in the developing tectum, the underlying mechanism and signaling cascade downstream of FGF remains unclear. Here, we showed that deleting Shp2, which links FGF with the ERK pathway, prevented inferior colliculus formation by depleting a previously uncharacterized stem cell zone, designated as tectal stem zone, in the posterior part of the developing tectum...
August 30, 2016: Development
Priya Saju, Naoko Murata-Kamiya, Takeru Hayashi, Yoshie Senda, Lisa Nagase, Saori Noda, Keisuke Matsusaka, Sayaka Funata, Akiko Kunita, Masayuki Urabe, Yasuyuki Seto, Masashi Fukayama, Atsushi Kaneda, Masanori Hatakeyama
Most if not all gastric cancers are associated with chronic infection of the stomach mucosa with Helicobacter pylori cagA-positive strains(1-4). Approximately 10% of gastric cancers also harbour Epstein-Barr virus (EBV) in the cancer cells(5,6). Following delivery into gastric epithelial cells via type IV secretion(7,8), the cagA-encoded CagA protein undergoes tyrosine phosphorylation on the Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs initially by Src family kinases (SFKs) and then by c-Abl(9,10). Tyrosine-phosphorylated CagA binds to the pro-oncogenic protein tyrosine phosphatase SHP2 and thereby deregulates the phosphatase activity(11,12), which has been considered to play an important role in gastric carcinogenesis(13)...
2016: Nature Microbiology
J Tao, L Zheng, M Meng, Y Li, Z Lu
Tyrosine phosphatase protein Shp2 is a potential therapeutic target for obesity. However, the mechanism of Shp2 during adipogenesis is not fully understood. The present study investigated the role of Shp2 in the terminal differentiation of preadipocytes. The results showed that Shp2 suppressed adipocyte differentiation in 3T3-L1 cells; overexpression of Shp2 reduced lipid droplet production in 3T3-L1 cells, whereas Shp2 knockdown increased lipid droplet production in 3T3-L1 cells. Furthermore, inhibition of Shp2 activity also enhanced adipocyte differentiation...
2016: Cell Death Discovery
Simon A Filson, Aviad Keren, Nyra Goldstein, Yehuda Ullmann
BACKGROUND: Fat grafting is an increasingly popular method of augmentation/reconstruction of soft tissue defects. However, the clinical unpredictability and high resorption rates of the grafts remain problematic. Cellular stress from the harvest and the ensuing ischemic episode may be the cause of this. Cellular stress activates the p38 mitogen-activated protein kinase (MAPK) signaling pathway. In response to cellular stress, the p38 pathway can lead to apoptosis and can negatively regulate cell proliferation...
July 2016: Plastic and Reconstructive Surgery. Global Open
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