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T cell signaling

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https://www.readbyqxmd.com/read/29793020/epha2-stimulates-vcam-1-expression-through-calcium-dependent-nfat1-activity
#1
Steven Daniel Funk, Alexandra C Finney, Arif Yurdagul, Christopher B Pattillo, A Wayne Orr
Endothelial cell activation by proinflammatory stimuli drives leukocyte recruitment through enhanced expression of counter-receptors such as vascular cell adhesion molecule-1 (VCAM-1). We previously demonstrated that activation of the receptor tyrosine kinase EphA2 with its ligand ephrin-A1 induces VCAM-1 expression. Here, we sought to characterize the proinflammatory signaling pathways involved. Analysis of over-represented transcription factors in ephrin-A1-induced genes identified multiple potential transcriptional regulators, including the Rel family members nuclear factor-κB (NF-κB/p65) and nuclear factor of activated T-cells (NFAT)...
May 21, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29792901/identification-and-functional-characterization-including-cytokine-production-modulation-of-the-novel-chicken-interleukin-11
#2
Anh Duc Truong, Yeojin Hong, Deivendran Rengaraj, Janggeun Lee, Kyungbaek Lee, Yeong Ho Hong
Interleukin (IL)-11 plays an important role in the immune system. However, IL-11 has not yet been characterized in avian species, including chickens. This study is the first to clone and functionally characterize chicken IL-11 (chIL-11). Multiple alignments and phylogenetic tree comparisons of chIL-11 with IL-11 proteins from other species revealed high levels of conservation and a close relationship between chicken and Japanese quail IL-11. Our results demonstrate that chIL-11 was a functional ligand of IL-11RA and IL-6ST in chicken HD11 and OU2 cell lines, as well as activated and regulated JAK-STAT, NF-κB, PI3K/AKT, and MAPK signaling pathways in chicken cell lines...
May 21, 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29792854/bergmann-glial-sonic-hedgehog-signaling-activity-is-required-for-proper-cerebellar-cortical-expansion-and-architecture
#3
Frances Y Cheng, Jonathan T Fleming, Chin Chiang
Neuronal-glial relationships play a critical role in the maintenance of central nervous system architecture and neuronal specification. A deeper understanding of these relationships can elucidate cellular cross-talk capable of sustaining proper development of neural tissues. In the cerebellum, cerebellar granule neuron precursors (CGNPs) proliferate in response to Purkinje neuron-derived Sonic hedgehog (Shh) before ultimately exiting the cell cycle and migrating radially along Bergmann glial fibers. However, the function of Bergmann glia in CGNP proliferation remains not well defined...
May 21, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29792808/eradication-of-established-tumors-by-chemically-self-assembled-nanoring-csan-targeted-t-cells
#4
Jacob Petersburg, Jingjing Shen, Clifford M Csizmar, Katherine A Murphy, Justin Spanier, Kari Gabrielse, Thomas S Griffith, Brian Fife, Carston R Wagner
Our laboratory has developed chemically self-assembled nanorings (CSANs) as prosthetic antigen receptors (PARs) for the non-genetic modification of T-cell surfaces. PARs have been successfully employed in vitro to activate T cells for the selective killing of leukemia cells. However, PAR efficacy has yet to be evaluated in vivo or against solid tumors. Therefore, we developed bispecific PARs that selectively target the human CD3 receptor and human Epithelial Cell Adhesion Molecule (EpCAM), which is overexpressed on multiple carcinomas and cancer stem cells...
May 24, 2018: ACS Nano
https://www.readbyqxmd.com/read/29792038/downregulation-of-cancer-stemness-by-novel-diterpenoid-ovatodiolide-inhibits-hepatic-cancer-stem-cell-like-traits-by-repressing-wnt-formula-see-text-catenin-signaling
#5
Mingche Liu, Oluwaseun Adebayo Bamodu, Kuang-Tai Kuo, Wei-Hwa Lee, Yen-Kuang Lin, Alexander T H Wu, Hsiao M, Yew-Min Tzeng, Chi-Tai Yeh, Jo-Ting Tsai
The hierarchical tumor propagation or cancer stem cells (CSCs) model of carcinogenesis postulates that like physiologic adult stem cell (ASC), the CSCs positioned at the apex of any tumor population form the crux of tumor evolution with a constitutive regenerative capacity and differentiation potential. The propagation and recurrence of the characteristically heterogeneous and therapy-resistant hepatocellular carcinoma (HCC), adds to accumulating evidence to support this CSCs model. Based on the multi-etiologic basis of HCC formation which among others, focuses on the disruption of the canonical Wnt signaling pathway, this study evaluated the role of cembrane-type phytochemical, Ovatodiolide, in the modulation of the Wnt/[Formula: see text]-catenin pathway, and its subsequent effect on liver CSCs' activities...
May 24, 2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29791894/highly-tumorigenic-diffuse-large-b-cell-lymphoma-cells-are-produced-by-coculture-with-stromal-cells
#6
Zhiguang Lin, Bobin Chen, Ting Wu, Xiaoping Xu
BACKGROUND/AIMS: Diffuse large B cell lymphoma (DLBCL) is heterogeneous. We aimed to explore how tumor microenvironment promotes lymphoma cell aggressiveness and heterogeneity. METHODS: We created a coculture system using human DLBCL cells and mouse bone marrow stromal cells. Proliferative capacity, drug resistance, clonogenicity, and tumorigenicity were compared in lymphoma cells from the coculture system and lymphoma cells cultured alone. Expression of Notch signaling associated genes was evaluated using real-time reverse transcriptase PCR and Western blot...
May 23, 2018: Acta Haematologica
https://www.readbyqxmd.com/read/29791856/activation-of-the-arterial-program-drives-development-of-definitive-hemogenic-endothelium-with-lymphoid-potential
#7
Mi Ae Park, Akhilesh Kumar, Ho Sun Jung, Gene Uenishi, Oleg V Moskvin, James A Thomson, Igor I Slukvin
Understanding the pathways guiding the development of definitive hematopoiesis with lymphoid potential is essential for advancing human pluripotent stem cell (hPSC) technologies for the treatment of blood diseases and immunotherapies. In the embryo, lymphoid progenitors and hematopoietic stem cells (HSCs) arise from hemogenic endothelium (HE) lining arteries but not veins. Here, we show that activation of the arterial program through ETS1 overexpression or by modulating MAPK/ERK signaling pathways at the mesodermal stage of development dramatically enhanced the formation of arterial-type HE expressing DLL4 and CXCR4...
May 22, 2018: Cell Reports
https://www.readbyqxmd.com/read/29791754/atp-triggers-a-robust-intracellular-ca-2-mediated-signalling-pathway-in-human-synovial-fibroblasts
#8
Kondo C, R B Clark, T Y Kim, Belke D, Banderali U, R T Szerencsei, A H Jalloul, P P M Schnetkamp, Spitzer Kw, Giles Wr
NEW FINDINGS: What is the central question of this study? In human articular joints, the synovial fibroblast HSF cell population has essential functions including secretion of lubricants. We address some remaining questions concerning activation-secretion coupling by characterizing the main [Ca2+ ]i signalling pathways activated by ATP. What is the main finding and its importance? In HSF ATP acts through a linked G-protein (Gq ) and phospholipase C signalling mechanisms to produce IP-3 which markedly enhances release of Ca2+ from the endoplasmic reticulum...
May 23, 2018: Experimental Physiology
https://www.readbyqxmd.com/read/29790605/cd57-identifies-t-cells-with-functional-senescence-before-terminal-differentiation-and-relative-telomere-shortening-in-patients-with-activated-pi3-kinase-delta-syndrome
#9
Paola Cura Daball, Monica Sofia Ventura Ferreira, Sandra Ammann, Christian Klemann, Myriam Ricarda Lorenz, Ursula Warthorst, T Ronan Leahy, Niall Conlon, Justin Roche, Pere Soler-Palacín, Marina Garcia-Prat, Ilka Fuchs, Sebastian Fuchs, Fabian Beier, Tim H Brümmendorf, Carsten Speckmann, Peter Olbrich, Olaf Neth, Klaus Schwarz, Stephan Ehl, Anne Rensing-Ehl
Premature T cell immunosenescence with CD57+ CD8+ T cell accumulation has been linked to immunodeficiency and autoimmunity in primary immunodeficiencies including activated PI3 kinase delta syndrome (APDS). To address whether CD57 marks the typical senescent T cell population seen in adult individuals or identifies a distinct population in APDS, we compared CD57+ CD8+ T cells from mostly pediatric APDS patients to those of healthy adults with similarly prominent senescent T cells. CD57+ CD8+ T cells from APDS patients were less differentiated with more CD27+ CD28+ effector memory cells showing increased PD1 and Eomesodermin expression...
May 23, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29790086/testosterone-mediated-activation-of-androgenic-signalling-sustains-in-vitro-the-transformed-and-radioresistant-phenotype-of-rhabdomyosarcoma-cell-lines
#10
S Giannattasio, F Megiorni, V Di Nisio, A Del Fattore, R Fontanella, S Camero, C Antinozzi, C Festuccia, G L Gravina, S Cecconi, C Dominici, L Di Luigi, C Ciccarelli, P De Cesaris, A Riccioli, B M Zani, A Lenzi, R G Pestell, A Filippini, C Crescioli, V Tombolini, F Marampon
PURPOSE: Rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in childhood, rarely affects adults, preferring male. RMS expresses the receptor for androgen (AR) and responds to androgen; however, the molecular action of androgens on RMS is unknown. METHODS: Herein, testosterone (T) effects were tested in embryonal (ERMS) and alveolar (ARMS) RMS cell lines, by performing luciferase reporter assay, RT-PCR, and western blotting experiments. RNA interference experiments or bicalutamide treatment was performed to assess the specific role of AR...
May 22, 2018: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/29789755/regulatory-mechanisms-in-t-cell-receptor-signalling
#11
REVIEW
Guillaume Gaud, Renaud Lesourne, Paul E Love
The remarkable T cell receptor (TCR) performs essential functions in the initiation of intracellular signals required for T cell development, repertoire selection and effector responses to foreign antigens. How TCR signals elicit such diverse cellular responses and outcomes remains a major question for investigation. Recent years have witnessed important advances in our understanding of the regulatory processes that control and modulate the TCR signalling response. Here, we review newly identified mechanisms for the regulation of TCR signalling and then discuss how the TCR signalling response is regulated to control two critical cellular processes - namely, positive selection and T cell homeostasis...
May 22, 2018: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/29789661/a-correlative-and-quantitative-imaging-approach-enabling-characterization-of-primary-cell-cell-communication-case-of-human-cd4-t-cell-macrophage-immunological-synapses
#12
Richard Kasprowicz, Emma Rand, Peter J O'Toole, Nathalie Signoret
Cell-to-cell communication engages signaling and spatiotemporal reorganization events driven by highly context-dependent and dynamic intercellular interactions, which are difficult to capture within heterogeneous primary cell cultures. Here, we present a straightforward correlative imaging approach utilizing commonly available instrumentation to sample large numbers of cell-cell interaction events, allowing qualitative and quantitative characterization of rare functioning cell-conjugates based on calcium signals...
May 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29789655/cigarette-smoke-promotes-hiv-infection-of-primary-bronchial-epithelium-and-additively-suppresses-cftr-function
#13
S Chinnapaiyan, R Dutta, J Bala, T Parira, M Agudelo, M Nair, H J Unwalla
Recurrent lung infections are a common cause of morbidity and mortality in people living with HIV and this is exacerbated in smokers even when administered combination antiretroviral therapy (cART). The incidence of pneumonia is increased with smoking and treatment interruption and is directly dependent on viral load in patients when adjusted for CD4 counts. CFTR dysfunction plays an important role in aberrant airway innate immunity as it is pivotal in regulating mucociliary clearance (MCC) rates and other antibacterial mechanisms of the airway...
May 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29789630/preclinical-evaluation-of-ribociclib-and-its-synergistic-effect-in-combination-with-alpelisib-in-non-keratinizing-nasopharyngeal-carcinoma
#14
Chi-Hang Wong, Brigette B Y Ma, Connie W C Hui, Kwok-Wai Lo, Edwin P Hui, Anthony T C Chan
Ribociclib is a specific cyclin dependent kinase (Cdk) 4/6 inhibitor that induces G1 arrest by blocking the formation of cyclin D1-Cdk4/6 complex and inhibiting retinoblastoma (RB) phosphorylation. Cyclin D1 is overexpressed in over 90% of nasopharyngeal carcinoma (NPC) and CCND1 gene activation plays a critical role in NPC pathogenesis. This study evaluated the preclinical activities of ribociclib in NPC cell lines and patient derived xenograft (PDX) models. Over 95% cell growth inhibition was observed at 96 hours after ribociclib treatment...
May 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29789608/downregulation-of-endothelin-receptor-b-contributes-to-defective-b-cell-lymphopoiesis-in-trisomy-21-pluripotent-stem-cells
#15
Glenn A MacLean, Jennifer McEldoon, Jialiang Huang, Jeremy Allred, Matthew C Canver, Stuart H Orkin
Individuals with Trisomy 21 (T21) exhibit numerous hematological abnormalities, including reductions in numbers of circulating B and T lymphocytes. To elucidate molecular mechanisms underlying these phenotypes, we differentiated human isogenic disomic and trisomic pluripotent cells, and observed that trisomic cells showed defects in B cell, but not T cell differentiation. Global gene expression of differentiated, trisomic B cells revealed reduced expression of genes encoding endothelin signaling components, namely the Endothelin Receptor B (EDNRB), and its ligand Endothelin1 (EDN1)...
May 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29789418/juxtacrine-signaling-inhibits-antitumor-immunity-by-upregulating-pd-l1-expression
#16
Wen-Hao Yang, Jong-Ho Cha, Weiya Xia, Heng-Huan Lee, Li-Chuan Chan, Ying-Nai Wang, Jennifer L Hsu, Guoxin Ren, Mien-Chie Hung
Programmed death-ligand 1 (PD-L1) is a well-known immune checkpoint protein that helps cancer cells evade immune response. Anti-PD-L1 immune therapy has been approved for the treatment of several advanced human cancers. Therefore, further understanding of the regulatory mechanisms of PD-L1 is critical to improve PD-L1-targeting immunotherapy. Recent studies indicated that contact-dependent pathways may regulate anticancer immunity, highlighting the importance of cell contact-induced signaling in cancer immunity...
May 22, 2018: Cancer Research
https://www.readbyqxmd.com/read/29789297/the-duf1669-domain-of-fam83-family-proteins-anchor-casein-kinase-1-isoforms
#17
Luke J Fulcher, Polyxeni Bozatzi, Theresa Tachie-Menson, Kevin Z L Wu, Timothy D Cummins, Joshua C Bufton, Daniel M Pinkas, Karen Dunbar, Sabin Shrestha, Nicola T Wood, Simone Weidlich, Thomas J Macartney, Joby Varghese, Robert Gourlay, David G Campbell, Kevin S Dingwell, James C Smith, Alex N Bullock, Gopal P Sapkota
Members of the casein kinase 1 (CK1) family of serine-threonine protein kinases are implicated in the regulation of many cellular processes, including the cell cycle, circadian rhythms, and Wnt and Hedgehog signaling. Because these kinases exhibit constitutive activity in biochemical assays, it is likely that their activity in cells is controlled by subcellular localization, interactions with inhibitory proteins, targeted degradation, or combinations of these mechanisms. We identified members of the FAM83 family of proteins as partners of CK1 in cells...
May 22, 2018: Science Signaling
https://www.readbyqxmd.com/read/29789296/tuning-itam-multiplicity-on-t-cell-receptors-can-control-potency-and-selectivity-to-ligand-density
#18
John R James
The T cell antigen receptor (TCR) recognizes peptides from pathogenic proteins bound in the major histocompatibility complex (MHC). To convert this binding event into downstream signaling, the TCR complex contains immunoreceptor tyrosine-based activation motifs (ITAMs) that act as docking sites for the cytoplasmic tyrosine kinase ZAP-70. Unique among antigen receptors, the TCR complex uses 10 ITAMs to transduce peptide-MHC binding to the cell interior. Using synthetic, drug-inducible receptor-ligand pairs, it was found that greater ITAM multiplicity primarily enhanced the efficiency with which ligand binding was converted into an intracellular signal...
May 22, 2018: Science Signaling
https://www.readbyqxmd.com/read/29789295/integration-of-protein-phosphorylation-acetylation-and-methylation-data-sets-to-outline-lung-cancer-signaling-networks
#19
Mark Grimes, Benjamin Hall, Lauren Foltz, Tyler Levy, Klarisa Rikova, Jeremiah Gaiser, William Cook, Ekaterina Smirnova, Travis Wheeler, Neil R Clark, Alexander Lachmann, Bin Zhang, Peter Hornbeck, Avi Ma'ayan, Michael Comb
Protein posttranslational modifications (PTMs) have typically been studied independently, yet many proteins are modified by more than one PTM type, and cell signaling pathways somehow integrate this information. We coupled immunoprecipitation using PTM-specific antibodies with tandem mass tag (TMT) mass spectrometry to simultaneously examine phosphorylation, methylation, and acetylation in 45 lung cancer cell lines compared to normal lung tissue and to cell lines treated with anticancer drugs. This simultaneous, large-scale, integrative analysis of these PTMs using a cluster-filtered network (CFN) approach revealed that cell signaling pathways were outlined by clustering patterns in PTMs...
May 22, 2018: Science Signaling
https://www.readbyqxmd.com/read/29788929/resveratrol-induces-autophagy-dependent-apoptosis-in-hl-60-cells
#20
Yingying Fan, Jen-Fu Chiu, Jing Liu, Yan Deng, Cheng Xu, Jun Zhang, Guanwu Li
BACKGROUND: All known mechanisms of apoptosis induced by resveratrol act through cell cycle arrest and changes in mitochondrial membrane potential. It is currently unknown whether resveratrol-induced apoptosis is associated with other physiological processes, such as autophagy. METHODS: Apoptosis-related markers involved in the intrinsic and extrinsic apoptotic pathways, and autophagic markers were detected by using western blotting and immunofluorescence. Mitochondrial membrane potential was assayed by flow cytometry...
May 22, 2018: BMC Cancer
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