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Adaptor protein 2

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https://www.readbyqxmd.com/read/28639322/tnf-%C3%AE-induced-nod2-and-rip2-contribute-to-the-up-regulation-of-cytokines-induced-by-mdp-in-monocytic-thp-1-cells
#1
Xiaobin Chen, Zhilin Xiao, Xiumei Xie, Xueting Liu, Manli Jiang, Chuang Yuan, Li Yang, Jinyue Hu
Nucleotide-binding oligomerization domain containing 2 (NOD2)-induced signal transduction and cytokine production is regulated by a number of factors. However, the feedback effect of the pro-inflammatory TNF-α on NOD2-induced inflammation is not fully understood. In this study, we found unexpectedly that TNF-α up-regulated NOD2 ligand MDP-induced production of the CXC chemokines, including CXCL1, 2 and 8, and the pro-inflammatory cytokines, including IL-1β, IL-6 and TNF-α, in a dose-dependent manner at both mRNA and protein levels in monocytic THP-1 cells...
June 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28638935/jip1-and-jip3-cooperate-to-mediate-trkb-anterograde-axonal-transport-by-activating-kinesin-1
#2
Tao Sun, Yuan Li, Ting Li, Huixian Ma, Yunyun Guo, Xingyu Jiang, Ming Hou, Shuhong Huang, Zheyu Chen
Long-range anterograde axonal transport of TrkB is important for neurons to exert appropriate BDNF responses. TrkB anterograde axonal delivery is mediated by kinesin-1, which associates with TrkB via the adaptor protein JIP3 or the Slp1/Rab27B/CRMP-2 protein complex. However, little is known about the activation mechanisms of TrkB-loaded kinesin-1. Here, we show that JIP1 mediates TrkB anterograde axonal transport using JIP1 knockout mice, sciatic nerve ligation analysis and live imaging. Next, we proved that JIP1 and JIP3 cooperate to mediate TrkB anterograde axonal transport...
June 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28634176/impact-of-glycemic-variability-on-chromatin-remodeling-oxidative-stress-and-endothelial-dysfunction-in-type-2-diabetic-patients-with-target-hba1c-levels
#3
Sarah Costantino, Francesco Paneni, Rodolfo Battista, Lorenzo Castello, Giuliana Capretti, Sergio Chiandotto, Luigi Tanese, Giulio Russo, Dario Pitocco, Gaetano A Lanza, Massimo Volpe, Thomas F Lüscher, Francesco Cosentino
Intensive glycemic control (IGC) targeting HbA1c fails to show an unequivocal reduction of macrovascular complications in type 2 diabetes (T2D), however the underlining mechanisms remain elusive. Epigenetic changes are emerging as important mediators of cardiovascular damage and may play a role in this setting. This study investigates whether epigenetic regulation of the adaptor protein p66(Shc), a key driver of mitochondrial oxidative stress, contributes to persistent vascular dysfunction in T2D patients despite IGC...
June 20, 2017: Diabetes
https://www.readbyqxmd.com/read/28630139/functional-interfaces-between-ticam-2-tram-and-ticam-1-trif-in-tlr4-signaling
#4
REVIEW
Kenji Funami, Misako Matsumoto, Hiroyuki Oshiumi, Fuyuhiko Inagaki, Tsukasa Seya
Toll-like receptor 4 (TLR4) recognizes lipopolysaccharide (LPS), produces pro-inflammatory cytokines and type I interferons, and associates with a trigger of endotoxin shock. TLR4 is interacted with a TIR domain-containing adaptor molecule-2 (TICAM-2)/TRAM [TRIF (TIR domain-containing adaptor-inducing interferon-β)-related adaptor molecule] via its Toll-interleukin-1 receptor homology (TIR) domain. TICAM-2 acts as a scaffold protein and activates TIR domain-containing adaptor molecule-1 (TICAM-1)/TRIF. According to the structural analysis by NMR, TICAM-2 interacts with TICAM-1 by the acidic amino acids motif, E87/D88/D89...
June 19, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28628927/curcumin-promotes-apoptosis-of-activated-hepatic-stellate-cells-by-inhibiting-protein-expression-of-the-myd88-pathway
#5
Ya-Jun He, Kenny Kuchta, Yan-Mei Deng, Silke Cameron, Yu Lin, Xu-You Liu, Guo-Ron Ye, Xia Lv, Yuta Kobayashi, Jian-Chang Shu
Activation and proliferation of hepatic stellate cells (HSC) play an important role in the progress of liver fibrosis. HSC activation occurs in response to inflammatory cytokines, cellular interactions with immune cells, and morphogenetic signals. The literature hints to a role of the adaptor protein MyD88 in fibrosis. Although curcumin has been shown to exert inhibitory effects on the proliferation of HSC in vitro, its influence on the MyD88 pathway in HSC has remained unclear. Here, we investigated whether curcumin accelerates apoptosis of HSC through the MyD88 pathway...
June 19, 2017: Planta Medica
https://www.readbyqxmd.com/read/28626024/intersectin-2-controls-actin-cap-formation-and-meiotic-division-in-mouse-oocytes-through-the-cdc42-pathway
#6
Jiaqi Zhang, Rujun Ma, Ling Li, Lina Wang, Xiaojing Hou, Longsen Han, Juan Ge, Mo Li, Qiang Wang
Intersectins (ITSNs), an evolutionarily conserved adaptor protein family, have been implicated in multiple biologic processes; however, their functions in mammalian oocytes have not been addressed. Here, we report delayed meiotic resumption and defective cytokinesis upon specific depletion of ITSN2 in mouse oocytes. In particular, abnormal spindle, misaligned chromosomes, and loss of cortical actin cap are readily observed in ITSN2-depleted oocytes. Similarly, a small molecule that targets the Cdc42-ITSN interaction also disrupts oocyte maturation and actin polymerization...
June 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28623125/chronic-intermittent-hypoxia-induces-liver-fibrosis-in-mice-with-diet-induced-obesity-via-tlr4-myd88-mapk-nf-kb-signaling-pathways
#7
Hyeon Hui Kang, In Kyoung Kim, Hye In Lee, Hyonsoo Joo, Jeong Uk Lim, Jongmin Lee, Sang Haak Lee, Hwa Sik Moon
Obstructive sleep apnea (OSA) is associated with nonalcoholic fatty liver disease (NAFLD), and causes chronic intermittent hypoxia (CIH) during sleep. Inflammation is associated with the development of metabolic complications induced by CIH. Research suggests that innate immune mechanisms are involved in the pro-inflammatory pathways of liver fibrosis. The purpose of this study was to investigate whether innate immune responses induce liver fibrosis, and to evaluate mechanisms underlying hepatic inflammation related to CIH in a murine diet-induced obesity (DIO) model...
June 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28621666/9%C3%A3-structure-of-the-copi-coat-reveals-that-the-arf1-gtpase-occupies-two-contrasting-molecular-environments
#8
Svetlana O Dodonova, Patrick Aderhold, Juergen Kopp, Iva Ganeva, Simone Röhling, Wim J Hagen, Irmgard Sinning, Felix Wieland, John Ag Briggs
COPI coated vesicles mediate trafficking within the Golgi apparatus and between the Golgi and the endoplasmic reticulum. Assembly of a COPI coated vesicle is initiated by the small GTPase Arf1 that recruits the coatomer complex to the membrane, triggering polymerization and budding. The vesicle uncoats before fusion with a target membrane. Coat components are structurally conserved between COPI and clathrin/adaptor proteins. Using cryo-electron tomography and subtomogram averaging, we determined the structure of the COPI coat assembled on membranes in vitro at 9 Å resolution...
June 16, 2017: ELife
https://www.readbyqxmd.com/read/28619886/tubular-clathrin-ap-2-lattices-pinch-collagen-fibers-to-support-3d-cell-migration
#9
Nadia Elkhatib, Enzo Bresteau, Francesco Baschieri, Alba López Rioja, Guillaume van Niel, Stéphane Vassilopoulos, Guillaume Montagnac
Migrating cells often use focal adhesions in order to move. Focal adhesions are less prominent in cells migrating in three-dimensional (3D) as compared with 2D environments. We looked for alternative adhesion structures supporting cell migration. We analyzed the dynamics of clathrin-coated pits in cells migrating in a 3D environment of collagen fibers. Both topological cues and local engagement of integrins triggered the accumulation of clathrin-coated structures on fibers. Clathrin/adaptor protein 2 (AP-2) lattices pinched collagen fibers by adopting a tube-like morphology and regulated adhesion to fibers in an endocytosis-independent manner...
June 16, 2017: Science
https://www.readbyqxmd.com/read/28611190/cbl-family-e3-ubiquitin-ligases-control-jak2-ubiquitination-and-stability-in-hematopoietic-stem-cells-and-myeloid-malignancies
#10
Kaosheng Lv, Jing Jiang, Ryan Donaghy, Christopher R Riling, Ying Cheng, Vemika Chandra, Krasimira Rozenova, Wei An, Bhopal C Mohapatra, Benjamin T Goetz, Vinodh Pillai, Xu Han, Emily A Todd, Grace R Jeschke, Wallace Y Langdon, Suresh Kumar, Elizabeth O Hexner, Hamid Band, Wei Tong
Janus kinase 2 (JAK2) is a central kinase in hematopoietic stem/progenitor cells (HSPCs), and its uncontrolled activation is a prominent oncogenic driver of hematopoietic neoplasms. However, molecular mechanisms underlying the regulation of JAK2 have remained elusive. Here we report that the Casitas B-cell lymphoma (CBL) family E3 ubiquitin ligases down-regulate JAK2 stability and signaling via the adaptor protein LNK/SH2B3. We demonstrated that depletion of CBL/CBL-B or LNK abrogated JAK2 ubiquitination, extended JAK2 half-life, and enhanced JAK2 signaling and cell growth in human cell lines as well as primary murine HSPCs...
June 13, 2017: Genes & Development
https://www.readbyqxmd.com/read/28609762/increased-toll-like-receptor-myeloid-differentiation-factor-88-expression-at-the-maternal-fetal-interface-is-associated-with-spontaneous-abortion
#11
Mengzhou He, Yuan Zhou, Min Jiang, Fanfan Li, Meitao Yang, Yao Fan, Dongrui Deng
AIMS: Toll-like receptors (TLRs) form a group of pattern recognition receptors that play a major role in maintaining innate host immunity. Myeloid differentiation factor 88 (MyD88) is an adaptor molecule that is essential for signaling via the TLR family. To analyze the mechanism of the imbalance in the innate immune system mediated by TLRs-MyD88 in spontaneous abortion, we detected the expression of TLR-2, TLR-4, TLR-7, and MyD88 in placentae and deciduas. METHODS: The expression of TLR-2, TLR-4, TLR-7, and MyD88 in the placentae and deciduas of abortion-prone mice (n = 10) and normal pregnant mice (n = 10) were analyzed by immunochemistry, western blot, and real-time polymerase chain reaction...
June 14, 2017: Gynecologic and Obstetric Investigation
https://www.readbyqxmd.com/read/28598236/destructive-cellular-paths-underlying-familial-and-sporadic-parkinson-disease-converge-on-mitophagy
#12
Xinnan Wang
The knowledge gap separating the molecular and cellular underpinnings of Parkinson disease (PD) and its pathology hinders treatment innovation. Adding to this difficulty is the lack of a reliable biomarker for PD. Our previous studies identify a link of 2 PD proteins, PINK1 and PRKN/Parkin to a mitochondrial motor/adaptor RHOT1/Miro-1, which mediates mitochondrial motility and mitophagy. Here we review our recent paper showing that a third PD protein, LRRK2, also targets RHOT1 and regulates mitophagy, and pathogenic LRRK2 disrupts this function...
June 9, 2017: Autophagy
https://www.readbyqxmd.com/read/28592841/lipopolysaccharides-induced-inflammatory-responses-and-electrophysiological-dysfunctions-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#13
Gökhan Yücel, Zhihan Zhao, Ibrahim El-Battrawy, Huan Lan, Siegfried Lang, Xin Li, Fanis Buljubasic, Wolfram-Hubertus Zimmermann, Lukas Cyganek, Jochen Utikal, Ursula Ravens, Thomas Wieland, Martin Borggrefe, Xiao-Bo Zhou, Ibrahim Akin
Severe infections like sepsis lead frequently to cardiomyopathy. The mechanisms are unclear and an optimal therapy for septic cardiomyopathy still lacks. The aim of this study is to establish an endotoxin-induced inflammatory model using human induced pluripotent stem cell (hiPSC) derived cardiomyocytes (hiPSC-CMs) for mechanistic and therapeutic studies. hiPSC-CMs were treated by lipopolysaccharide (LPS) in different concentrations for different times. ELISA, FACS, qPCR, and patch-clamp techniques were used for the study...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28585318/hermansky-pudlak-syndrome-type-2-aberrant-pre-mrna-splicing-and-mislocalization-of-granule-proteins-in-neutrophils
#14
Martin de Boer, Karin van Leeuwen, Judy Geissler, Floris van Alphen, Esther de Vries, Martijn van der Kuip, Suzanne W J Terheggen, Hans Janssen, Timo K van den Berg, Alexander B Meijer, Dirk Roos, Taco W Kuijpers
Hermansky-Pudlak syndrome type 2 (HPS2) is a syndrome caused by mutations in the beta-3A subunit of the adaptor protein (AP)-3 complex (AP3B1 gene). We describe five unreported cases with four novel mutations, one of which caused aberrant pre-mRNA splicing. A point mutation c.2702C>G in exon 23 of the AP3B1 gene caused deletion of 112 bp in the mRNA in two siblings. This mutation activates a cryptic donor splice site that overrules the wild-type donor splice site of this exon. Three other novel mutations in AP3B1 were identified, that is, a nonsense mutation c...
June 6, 2017: Human Mutation
https://www.readbyqxmd.com/read/28577469/the-interaction-between-hiv-1-nef-and-adaptor-protein-2-reduces-nef-mediated-cd4-t-cell-apoptosis
#15
Rajesh Abraham Jacob, Aaron L Johnson, Emily N Pawlak, Brennan S Dirk, Logan R Van Nynatten, S M Mansour Haeryfar, Jimmy D Dikeakos
Acquired Immune Deficiency Syndrome is characterized by a decline in CD4(+) T cells. Here, we elucidated the mechanism underlying apoptosis in Human Immunodeficiency Virus-1 (HIV-1) infection by examining host apoptotic pathways hijacked by the HIV-1 Nef protein in the CD4(+) T-cell line Sup-T1. Using a panel of Nef mutants unable to bind specific host proteins we uncovered that Nef generates pro- and anti-apoptotic signals. Apoptosis increased upon mutating the motifs involved in the interaction of Nef:AP-1 (NefM20A or NefEEEE62-65AAAA) or Nef:AP-2 (NefLL164/165AA), implying these interactions limit Nef-mediated apoptosis...
May 31, 2017: Virology
https://www.readbyqxmd.com/read/28572508/cardioprotective-role-of-traf2-by-suppressing-apoptosis-and-necroptosis
#16
Xiaoyun Guo, Haifeng Yin, Lei Li, Yi Chen, Jing Li, Jessica Doan, Rachel N Steinmetz, Qinghang Liu
Background -Programed cell death, including apoptosis, mitochondria-mediated necrosis, and necroptosis, is critically involved in ischemic cardiac injury, pathological cardiac remodeling, and heart failure progression. Whereas apoptosis and mitochondria-mediated necrosis signaling is well established, the regulatory mechanisms of necroptosis and its significance in the pathogenesis of heart failure remain elusive. Methods -We examined the role of Traf2 (TNF receptor-associated factor 2) in regulating myocardial necroptosis and remodeling using genetic mouse models...
June 1, 2017: Circulation
https://www.readbyqxmd.com/read/28558797/expression-of-signaling-adaptor-proteins-predicts-poor-prognosis-in-pancreatic-ductal-adenocarcinoma
#17
Lili Wang, Junliang Lu, Huanwen Wu, Li Wang, Xiaolong Liang, Zhiyong Liang, Tonghua Liu
BACKGROUND: Adaptor proteins bridge the gap between cell surface receptors and their downstream signaling elements. The clinicopathological and prognostic values of adaptor proteins remain poorly understood. The purpose of the present study was to explore the expression and prognostic value of three adaptor proteins: GRB2-associated binding protein 2 (GAB2), CRK-like protein (CRKL) and fibroblast growth factor receptor substrate 2 (FRS2) in pancreatic ductal adenocarcinoma (PDAC). METHODS: The expression of GAB2, CRKL, and FRS2 in 77 formalin fixed paraffin embedded (FFPE) samples from 77 PDAC patients, along with three paired fresh PDAC and matched normal tissues from 3 PDAC patients was analyzed by immunohistochemistry and western blot, respectively...
May 30, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28553201/fe65-ptb2-dimerization-mimics-fe65-app-interaction
#18
Lukas P Feilen, Kevin Haubrich, Paul Strecker, Sabine Probst, Simone Eggert, Gunter Stier, Irmgard Sinning, Uwe Konietzko, Stefan Kins, Bernd Simon, Klemens Wild
Physiological function and pathology of the Alzheimer's disease causing amyloid precursor protein (APP) are correlated with its cytosolic adaptor Fe65 encompassing a WW and two phosphotyrosine-binding domains (PTBs). The C-terminal Fe65-PTB2 binds a large portion of the APP intracellular domain (AICD) including the GYENPTY internalization sequence fingerprint. AICD binding to Fe65-PTB2 opens an intra-molecular interaction causing a structural change and altering Fe65 activity. Here we show that in the absence of the AICD, Fe65-PTB2 forms a homodimer in solution and determine its crystal structure at 2...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28547529/toll-like-receptor-4-tlr4-and-triggering-receptor-expressed-on-myeloid-cells-2-trem-2-activation-balance-astrocyte-polarization-into-a-proinflammatory-phenotype
#19
Gerardo Rosciszewski, Vanesa Cadena, Veronica Murta, Jeronimo Lukin, Alejandro Villarreal, Thierry Roger, Alberto Javier Ramos
Astrocytes react to brain injury with a generic response known as reactive gliosis, which involves activation of multiple intracellular pathways including several that may be beneficial for neuronal survival. However, by unknown mechanisms, reactive astrocytes can polarize into a proinflammatory phenotype that induces neurodegeneration. In order to study reactive gliosis and astroglial polarization into a proinflammatory phenotype, we used cortical devascularization-induced brain ischemia in Wistar rats and primary astroglial cell cultures exposed to oxygen-glucose deprivation (OGD)...
May 25, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28544681/tenebrio-molitor-gram-negative-binding-protein-3-tmgnbp3-is-essential-for-inducing-downstream-antifungal-tenecin-1-gene-expression-against-infection-with-beauveria-bassiana-jef-007
#20
Yi-Ting Yang, Mi Rong Lee, Se Jin Lee, Sihyeon Kim, Yu-Shin Nai, Jae Su Kim
The Toll signaling pathway is responsible for defense against both Gram-positive bacteria and fungi. Gram-negative binding protein 3 (GNBP3) has a strong affinity for the fungal cell wall component, β-1,3-glucan, which can activate the prophenoloxidase (proPO) cascade and induce the Toll signaling pathway. Myeloid differentiation factor 88 (MyD88) is an intracellular adaptor protein involved in the Toll signaling pathway. In this study, we monitored the response of 5 key genes (TmGNBP3, TmMyD88, and Tenecin 1, 2, and 3) in the Toll pathway of the mealworm Tenebrio molitor immune system against the fungus Beauveria bassiana JEF-007 using RT-PCR...
May 23, 2017: Insect Science
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