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https://www.readbyqxmd.com/read/28539628/low-level-of-lck-kinase-in-th2-cells-limits-expression-of-cd4-co-receptor-and-s73-phosphorylation-of-transcription-factor-c-jun
#1
Yury V Shebzukhov, Silke Stanislawiak, Taisiya R Bezhaeva, Sergei A Nedospasov, Dmitry V Kuprash
The Src-family tyrosine kinase Lck is an enzyme associated with the CD4 and CD8 co-receptors and promoting signaling through the T cell receptor (TCR) complex. The levels of Lck expression and activity change during the development and differentiation of T cells. Here we show that Lck expression is higher in Th1 cells as compared to Th2 cells. Ectopic overexpression of Lck in Th2 cells results in increased expression of CD4 co-receptor and enhanced S73 phosphorylation of transcription factor c-Jun. Our findings indicate that TCR-mediated signaling in Th2 cells may be directly attenuated by Lck protein expression level...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28522807/traf3-enhances-tcr-signaling-by-regulating-the-inhibitors-csk-and-ptpn22
#2
Alicia M Wallis, Ellie C Wallace, Bruce S Hostager, Zuoan Yi, Jon C D Houtman, Gail A Bishop
The adaptor protein TNF receptor associated factor (TRAF) 3 is required for effective TCR signaling and normal T cell effector functions, and associates with the CD3/CD28 complex upon activation. To determine how TRAF3 promotes proximal TCR signaling, we studied TRAF3-deficient mouse and human T cells, which showed a marked reduction in activating phosphorylation of the TCR-associated kinase Lck. The impact of TRAF3 on this very early signaling event led to the hypothesis that TRAF3 restrains one or both of two known inhibitors of Lck, C-terminal Src kinase (Csk) and protein tyrosine phosphatase N22 (PTPN22)...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28516764/an-autoinhibitory-role-for-the-pleckstrin-homology-domain-of-interleukin-2-inducible-tyrosine-kinase-and-its-interplay-with-canonical-phospholipid-recognition
#3
Sujan Devkota, Raji E Joseph, Scott E Boyken, D Bruce Fulton, Amy H Andreotti
Pleckstrin homology (PH) domains are well-known as phospholipid binding modules, yet evidence that PH domain function extends beyond lipid recognition is mounting. In this work, we characterize a protein binding function for the PH domain of interleukin-2-inducible tyrosine kinase (ITK), an immune cell specific signaling protein that belongs to the TEC family of nonreceptor tyrosine kinases. Its N-terminal PH domain is a well-characterized lipid binding module that localizes ITK to the membrane via phosphatidylinositol 3,4,5-trisphosphate (PIP3) binding...
May 25, 2017: Biochemistry
https://www.readbyqxmd.com/read/28465009/crk-adaptor-proteins-regulate-cd3%C3%AE-chain-phosphorylation-and-tcr-cd3-down-modulation-in-activated-t-cells
#4
Guangyu Dong, Rachel Kalifa, Pulak Ranjan Nath, Yael Babichev, Sigal Gelkop, Noah Isakov
T cell receptor (TCR) recognition of a peptide antigen in the context of MHC molecules initiates positive and negative cascades that regulate T cell activation, proliferation and differentiation, and culminate in the acquisition of effector T cell functions. These processes are a prerequisite for the induction of specific T cell-mediated adaptive immune responses. A key event in the activation of TCR-coupled signaling pathways is the phosphorylation of tyrosine residues within the cytoplasmic tails of the CD3 subunits, predominantly CD3ζ...
April 29, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28462950/t-cell-activation-rhogtpase-activating-protein-plays-an-important-role-in-th17-cell-differentiation
#5
Norimasa Tamehiro, Kyoko Nishida, Reiko Yanobu-Takanashi, Motohito Goto, Tadashi Okamura, Harumi Suzuki
T-cell activation RhoGTPase-activating protein (TAGAP) is a GTPase-activating protein specific for RhoA that is exclusively expressed in activated T cells. Genome-wide association studies and metagenome SNPs analyses have indicated that TAGAP is associated with the pathogenesis of multiple autoimmune diseases, including psoriasis, rheumatoid arthritis, Crohn's disease, celiac disease and multiple sclerosis. However, the precise function of TAGAP remains unclear. Because TH17 cells contribute to TAGAP-associated autoimmune diseases, we hypothesized that TAGAP plays key roles in the differentiation and/or function of TH17 cells...
May 2, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28448599/simulation-of-the-dynamics-of-primary-immunodeficiencies-in-cd4-t-cells
#6
Gabriel N Teku, Mauno Vihinen
Primary immunodeficiencies (PIDs) form a large and heterogeneous group of mainly rare disorders that affect the immune system. T-cell deficiencies account for about one-tenth of PIDs, most of them being monogenic. Apart from genetic and clinical information, lots of other data are available for PID proteins and genes, including functions and interactions. Thus, it is possible to perform systems biology studies on the effects of PIDs on T-cell physiology and response. To achieve this, we reconstructed a T-cell network model based on literature mining and TPPIN, a previously published core T-cell network, and performed semi-quantitative dynamic network simulations on both normal and T-cell PID failure modes...
2017: PloS One
https://www.readbyqxmd.com/read/28445761/live-cell-super-resolution-reveals-f-actin-and-plasma-membrane-dynamics-at-the-t-cell-synapse
#7
George W Ashdown, Garth L Burn, David J Williamson, Elvis Pandžić, Ruby Peters, Michael Holden, Helge Ewers, Lin Shao, Paul W Wiseman, Dylan M Owen
The cortical actin cytoskeleton has been shown to be critical for the reorganization and heterogeneity of plasma membrane components of many cells, including T cells. Building on previous studies at the T cell immunological synapse, we quantitatively assess the structure and dynamics of this meshwork using live-cell superresolution fluorescence microscopy and spatio-temporal image correlation spectroscopy. We show for the first time, to our knowledge, that not only does the dense actin cortex flow in a retrograde fashion toward the synapse center, but the plasma membrane itself shows similar behavior...
April 25, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28424240/the-histone-acetyltransferase-gcn5-positively-regulates-t-cell-activation
#8
Beixue Gao, Qingfei Kong, Yana Zhang, Chawon Yun, Sharon Y R Dent, Jianxun Song, Donna D Zhang, Yiming Wang, Xuemei Li, Deyu Fang
Histone acetyltransferases (HATs) regulate inducible transcription in multiple cellular processes and during inflammatory and immune response. However, the functions of general control nonrepressed-protein 5 (Gcn5), an evolutionarily conserved HAT from yeast to human, in immune regulation remain unappreciated. In this study, we conditionally deleted Gcn5 (encoded by the Kat2a gene) specifically in T lymphocytes by crossing floxed Gcn5 and Lck-Cre mice, and demonstrated that Gcn5 plays important roles in multiple stages of T cell functions including development, clonal expansion, and differentiation...
May 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28416261/feasibility-study-of-personalized-peptide-vaccination-for-advanced-small-cell-lung-cancer
#9
Shinjiro Sakamoto, Teppei Yamada, Yasuhiro Terazaki, Koichi Yoshiyama, Shunichi Sugawara, Shinzo Takamori, Satoko Matsueda, Shigeki Shichijo, Akira Yamada, Masanori Noguchi, Kyogo Itoh, Noboru Hattori, Nobuoki Kohno, Tetsuro Sasada
INTRODUCTION: The prognosis of patients with small cell lung cancer (SCLC) remains very poor. Therefore, the development of new therapeutic approaches, including immunotherapies, is desirable. PATIENTS AND METHODS: We conducted a phase II study of personalized peptide vaccination (PPV), in which a maximum of 4 human leukocyte antigen-matched peptides were selected from 31 pooled peptides according to the pre-existing peptide-specific IgG responses before vaccination...
March 24, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28359287/activity-of-the-novel-bcr-kinase-inhibitor-iqs019-in-preclinical-models-of-b-cell-non-hodgkin-lymphoma
#10
P Balsas, A Esteve-Arenys, J Roldán, L Jiménez, V Rodríguez, J G Valero, A Chamorro-Jorganes, R Puig de la Bellacasa, J Teixidó, A Matas-Céspedes, A Moros, A Martínez, E Campo, A Sáez-Borderías, J I Borrell, P Pérez-Galán, D Colomer, G Roué
BACKGROUND: Pharmacological inhibition of B cell receptor (BCR) signaling has recently emerged as an effective approach in a wide range of B lymphoid neoplasms. However, despite promising clinical activity of the first Bruton's kinase (Btk) and spleen tyrosine kinase (Syk) inhibitors, a small fraction of patients tend to develop progressive disease after initial response to these agents. METHODS: We evaluated the antitumor activity of IQS019, a new BCR kinase inhibitor with increased affinity for Btk, Syk, and Lck/Yes novel tyrosine kinase (Lyn), in a set of 34 B lymphoid cell lines and primary cultures, including samples with acquired resistance to the first-in-class Btk inhibitor ibrutinib...
March 31, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28347651/selective-targeting-of-sh2-domain-phosphotyrosine-interactions-of-src-family-tyrosine-kinases-with-monobodies
#11
Tim Kükenshöner, Nadine Eliane Schmit, Emilie Bouda, Fern Sha, Florence Pojer, Akiko Koide, Markus Seeliger, Shohei Koide, Oliver Hantschel
The binding of Src-homology 2 (SH2) domains to phosphotyrosine (pY) sites is critical for the autoinhibition and substrate recognition of the eight Src family kinases (SFKs). The high sequence conservation of the 120 human SH2 domains poses a significant challenge to selectively perturb the interactions of even the SFK SH2 family against the rest of the SH2 domains. We have developed synthetic binding proteins, termed monobodies, for six of the SFK SH2 domains with nanomolar affinity. Most of these monobodies competed with pY ligand binding and showed strong selectivity for either the SrcA (Yes, Src, Fyn, Fgr) or SrcB subgroup (Lck, Lyn, Blk, Hck)...
May 5, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28333124/bap31-is-involved-in-t-cell-activation-through-tcr-signal-pathways
#12
Kunwei Niu, Jialin Xu, Yuhua Cao, Yue Hou, Mu Shan, Yanqing Wang, Yang Xu, Mingyi Sun, Bing Wang
BAP31 is a ubiquitously expressed endoplasmic reticulum (ER) membrane protein. The functions of BAP31 in the immune system have not been investigated due to the lack of animal models. Therefore we created a BAP31 conditional knockdown mouse by performing a knockdown of BAP31 in the thymus. In doing so, we demonstrate that the maturation of T cells is normal but the number of T cells is less in the thymus of the knockout mouse. In addition, the spleen and lymph nodes of peripheral immune organs contained a lesser proportion of the mature T cells in the thymus specific BAP31 knockout mice...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28316886/identification-of-dysregulated-genes-in-rheumatoid-arthritis-based-on-bioinformatics-analysis
#13
Ruihu Hao, Haiwei Du, Lin Guo, Fengde Tian, Ning An, Tiejun Yang, Changcheng Wang, Bo Wang, Zihao Zhou
BACKGROUND: Rheumatoid arthritis (RA) is a chronic auto-inflammatory disorder of joints. The present study aimed to identify the key genes in RA for better understanding the underlying mechanisms of RA. METHODS: The integrated analysis of expression profiling was conducted to identify differentially expressed genes (DEGs) in RA. Moreover, functional annotation, protein-protein interaction (PPI) network and transcription factor (TF) regulatory network construction were applied for exploring the potential biological roles of DEGs in RA...
2017: PeerJ
https://www.readbyqxmd.com/read/28286257/grouper-epinephelus-coioides-tcr-signaling-pathway-was-involved-in-response-against-cryptocaryon-irritans-infection
#14
Ze-Xiang Li, Yan-Wei Li, Shun Xu, Yang Xu, Ze-Quan Mo, Xue-Ming Dan, Xiao-Chun Luo
T cell activation is a complicated process accompanying with the activation of T cell receptor (TCR) signaling pathway, which is not well described in teleost fish. The initiation of this pathway depends on the interaction of membrane TCR co-receptors (e.g. CD4/8, CD3 and CD45) and a series of cytoplasmic protein tyrosine kinases (e.g. Lck, Fyn and ZAP70). Cyptocaryon irritans is a ciliate pathogen of marine fish white spot disease causing huge economic lost in marine aquaculture. This parasite can infect fish gill and skin and is considered to be a good pathogen model for fish gill and skin mucosal immunity...
May 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28278192/pbmc-transcriptome-profiles-identifies-potential-candidate-genes-and-functional-networks-controlling-the-innate-and-the-adaptive-immune-response-to-prrsv-vaccine-in-pietrain-pig
#15
Md Aminul Islam, Christine Große-Brinkhaus, Maren Julia Pröll, Muhammad Jasim Uddin, Sharmin Aqter Rony, Dawit Tesfaye, Ernst Tholen, Michael Hoelker, Karl Schellander, Christiane Neuhoff
The porcine reproductive and respiratory syndrome (PRRS) is a devastating viral disease affecting swine production, health and welfare throughout the world. A synergistic action of the innate and the adaptive immune system of the host is essential for mounting a durable protective immunity through vaccination. Therefore, the current study aimed to investigate the transcriptome profiles of peripheral blood mononuclear cells (PBMCs) to characterize the innate and the adaptive immune response to PRRS Virus (PRRSV) vaccination in Pietrain pigs...
2017: PloS One
https://www.readbyqxmd.com/read/28250239/src-family-kinases-in-hamster-spermatozoa-evidence-for-the-presence-of-lck
#16
Durgesh Kumar Singh, Rohit Kumar Deshmukh, Praveen Kumar Narayanan, Sisinthy Shivaji, Archana Bharadwaj Siva
Sperm capacitation is a prerequisite for successful fertilization. Increase in tyrosine phosphorylation is considered the hallmark of capacitation and attempts to understand its regulation are ongoing. In this regard, we attempted to study the role of SRC family kinases (SFKs) in the hamster sperm functions. Interestingly, we found the presence of the lymphocyte-specific protein tyrosine kinase, LCK, in mammalian spermatozoa and further characterized it in terms of its localization and function. LCK was found in spermatozoa of several species, and its transcript was identified in the hamster testis...
May 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28235866/rab11-fip3-regulation-of-lck-endosomal-traffic-controls-tcr-signal-transduction
#17
Jérôme Bouchet, Iratxe Del Río-Iñiguez, Elena Vázquez-Chávez, Rémi Lasserre, Sonia Agüera-González, Céline Cuche, Mary W McCaffrey, Vincenzo Di Bartolo, Andrés Alcover
The role of endosomes in receptor signal transduction is a long-standing question, which remains largely unanswered. The T cell Ag receptor and various components of its proximal signaling machinery are associated with distinct endosomal compartments, but how endosomal traffic affects T cell signaling remains ill-defined. In this article, we demonstrate in human T cells that the subcellular localization and function of the protein tyrosine kinase Lck depends on the Rab11 effector FIP3 (Rab11 family interacting protein-3)...
February 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28209773/mannan-binding-lectin-a-serum-collectin-suppresses-t-cell-proliferation-via-direct-interaction-with-cell-surface-calreticulin-and-inhibition-of-proximal-t-cell-receptor-signaling
#18
Na Zhao, Jie Wu, Simin Xiong, Liyun Zhang, Xiao Lu, Shangliang Chen, Qifeng Wu, Hailan Wang, Ying Liu, Zhengliang Chen, Daming Zuo
Mannan binding lectin (MBL), initially described to activate the complement pathway, is also known to be involved in the pathogenesis of autoimmune diseases. We report a thus far unknown function of MBL as a suppressor of T-cell activation. MBL markedly inhibited T-cell proliferation induced by anti-CD3 and anti-CD28 antibodies. Moreover, the presence of MBL during T-cell priming interfered with proximal T-cell receptor signaling by decreasing phosphorylation of Lck, ZAP-70, and LAT. MBL bound to T cells through interaction between the collagen-like region of MBL and calreticulin (CRT) expressed on the T-cell surface...
February 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28185804/7-cyclopentyl-5-4-phenoxyphenyl-7h-pyrrolo-2-3-d-pyrimidin-4-ylamine-inhibits-the-proliferation-and-migration-of-vascular-smooth-muscle-cells-by-suppressing-erk-and-akt-pathways
#19
Hyang-Hee Seo, Sang Woo Kim, Chang Youn Lee, Kyu Hee Lim, Jiyun Lee, Soyeon Lim, Seahyoung Lee, Ki-Chul Hwang
Excessive vascular smooth muscle cell (VSMC) proliferation and migration after vascular injury significantly contributes to the development of occlusive vascular disease. Therefore, inhibiting the proliferation and migration of VSMCs is a validated therapeutic modality for occlusive vascular disease such as atherosclerosis and restenosis. In the present study, we screened chemical compounds for their anti-proliferative effects on VSMCs using multiple approaches, such as MTT assays, wound healing assays, and trans-well migration assays...
March 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28175613/369%C3%A2-chimeric-antigen-receptors-deficient-in-lck-signaling-require-4-1bb-costimulation-to-expand-in-vivo-resist-regulatory-t-cell-suppression-and-treat-solid-tumors-in-immune-intact-hosts
#20
Carter M Suryadevara, Rupen Desai, Samuel Harrison Farber, Patrick C Gedeon, Adam Swartz, David Snyder, James Herndon, Patrick Healy, Bryan D Choi, Peter Edward Fecci, Luis Sanchez-Perez, John H Sampson
No abstract text is available yet for this article.
August 1, 2016: Neurosurgery
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