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https://www.readbyqxmd.com/read/27910998/aurora-a-shines-on-t-cell-activation-through-the-regulation-of-lck
#1
Noelia Blas-Rus, Eugenio Bustos-Morán, Noa B Martín-Cófreces, Francisco Sánchez-Madrid
Different protein kinases control signaling emanating from the T cell receptor (TCR) during antigen-specific T cell activation. Mitotic kinases, e.g. Aurora-A, have been widely studied in the context of mitosis due to their role during microtubule (MT) nucleation, becoming critical regulators of cell cycle progression. We have recently described a specific role for Aurora-A kinase in antigenic T cell activation. Blockade of Aurora-A in T cells severely disrupts the dynamics of MTs and CD3ζ-bearing signaling vesicles during T cell activation...
December 2, 2016: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/27908976/a-novel-method-for-culturing-stellate-astrocytes-reveals-spatially-distinct-ca2-signaling-and-vesicle-recycling-in-astrocytic-processes
#2
Anne C Wolfes, Saheeb Ahmed, Ankit Awasthi, Markus A Stahlberg, Ashish Rajput, Daniel S Magruder, Stefan Bonn, Camin Dean
Interactions between astrocytes and neurons rely on the release and uptake of glial and neuronal molecules. But whether astrocytic vesicles exist and exocytose in a regulated or constitutive fashion is under debate. The majority of studies have relied on indirect methods or on astrocyte cultures that do not resemble stellate astrocytes found in vivo. Here, to investigate vesicle-associated proteins and exocytosis in stellate astrocytes specifically, we developed a simple, fast, and economical method for growing stellate astrocyte monocultures...
December 1, 2016: Journal of General Physiology
https://www.readbyqxmd.com/read/27898263/genetic-alterations-affecting-gtpases-and-t-cell-receptor-signaling-in-peripheral-t-cell-lymphomas
#3
Rebecca L Boddicker, Gina L Razidlo, Andrew L Feldman
Peripheral T-cell lymphomas (PTCLs) are rare, heterogeneous tumors with poor response to standard therapy and few targeted treatments available. The identification of mutations in the T-cell receptor (TCR) signaling pathway that either directly or indirectly affect Ras- and Rho-family GTPases is an emerging theme across PTCL subtypes. This review summarizes the role of GTPases in TCR signaling and highlights the constellation of mutations in this pathway among PTCLs. In particular, focus is given to the functional impact of the mutations and opportunities for targeted therapy...
November 29, 2016: Small GTPases
https://www.readbyqxmd.com/read/27896837/cd6-and-linker-of-activated-t-cells-are-potential-interaction-partners-for-t-cell-specific-adaptor-protein
#4
Cecilie Dahl Hem, Marianne Ekornhol, Stine Granum, Vibeke Sundvold-Gjerstad, Anne Spurkland
The T cell specific adaptor protein (TSAd) contains several protein interaction domains, and is merging as a modulator of T cell activation. Several interaction partners for the TSAd proline rich region and phosphotyrosines have been identified, including the Src and Tec family kinases Lymphocyte specific protein tyrosine kinase (Lck) and Interleukin 2-Inducible T-cell kinase (Itk). Via its Src homology 2 (SH2) domain, TSAd may thus function as a link between these enzymes and other signaling molecules. However, few binding partners to the TSAd SH2 domain in T cells are hitherto known...
November 29, 2016: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/27864698/blk-pathway-associated-rs13277113-ga-genotype-is-more-frequent-in-sle-patients-and-associated-with-low-gene-expression-and-increased-flares
#5
Omer Nuri Pamuk, Hakan Gurkan, Gulsum Emel Pamuk, Hilmi Tozkır, Julide Duymaz, Metin Yazar
We aimed to evaluate the relationship between some important genetic variations and expressions of these genes in our SLE population. We also determined their association with clinical parameters. Eighty-four SLE patients (79 F, 5 M) and 105 healthy controls (98 F, 7 M) were included in the study. rs13277113, rs2736340, rs7829816, rs6983130, rs2613310, and rs704853 polymorphisms, gene expressions of Src family kinases (Blk, Hck, Lck, and Lyn), and Syk kinases (Syk, ZAP70) were studied by real-time PCR. The heterozygous genotypic pattern (GA) for rs13277113 polymorphism was more frequent in patients with SLE when compared to that in controls (48...
November 18, 2016: Clinical Rheumatology
https://www.readbyqxmd.com/read/27837109/characterization-of-the-syk-dependent-t-cell-signaling-response-to-an-altered-peptide
#6
Jeoung-Eun Park, Jeffrey A Rotondo, David L Cullins, David D Brand, Ae-Kyung Yi, John M Stuart, Andrew H Kang, Linda K Myers
Rheumatoid arthritis is an autoimmune disorder characterized by T cell dysregulation. We have shown that an altered peptide ligand (A9) activates T cells to use an alternate signaling pathway that is dependent on FcRγ and spleen tyrosine kinase, resulting in downregulation of inflammation. In the experiments described in this study, we have attempted to determine the molecular basis of this paradox. Three major Src family kinases found in T cells (Lck, Fyn, and Lyn) were tested for activation following stimulation by A9/I-A(q) Unexpectedly we found they are not required for T cell functions induced by A9/I-A(q), nor are they required for APL stimulation of cytokines...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27833610/tcr-triggering-induces-the-formation-of-lck-rack1-actinin-1-multiprotein-network-affecting-lck-redistribution
#7
Ondřej Ballek, Jan Valečka, Martina Dobešová, Adéla Broučková, Jasper Manning, Pavel Řehulka, Jiří Stulík, Dominik Filipp
The initiation of T-cell signaling is critically dependent on the function of the member of Src family tyrosine kinases, Lck. Upon T-cell antigen receptor (TCR) triggering, Lck kinase activity induces the nucleation of signal-transducing hubs that regulate the formation of complex signaling network and cytoskeletal rearrangement. In addition, the delivery of Lck function requires rapid and targeted membrane redistribution, but the mechanism underpinning this process is largely unknown. To gain insight into this process, we considered previously described proteins that could assist in this process via their capacity to interact with kinases and regulate their intracellular translocations...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27798165/hiv-1-nef-impairs-the-formation-of-calcium-membrane-territories-controlling-the-signaling-nanoarchitecture-at-the-immunological-synapse
#8
Joana G Silva, Nuno P Martins, Ricardo Henriques, Helena Soares
The ability of HIV-1 to replicate and to establish long-term reservoirs is strongly influenced by T cell activation. Through the use of membrane-tethered, genetically encoded calcium (Ca(2+)) indicators, we were able to detect for the first time, to our knowledge, the formation of Ca(2+) territories and determine their role in coordinating the functional signaling nanostructure of the synaptic membrane. Consequently, we report a previously unknown immune subversion mechanism involving HIV-1 exploitation, through its Nef accessory protein, of the interconnectivity among three evolutionarily conserved cellular processes: vesicle traffic, signaling compartmentalization, and the second messenger Ca(2+) We found that HIV-1 Nef specifically associates with the traffic regulators MAL and Rab11b compelling the vesicular accumulation of Lck...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27758892/e2a-pbx1-remodels-oncogenic-signaling-networks-in-b-cell-precursor-acute-lymphoid-leukemia
#9
Jesús Duque-Afonso, Chiou-Hong Lin, Kyuho Han, Michael C Wei, Jue Feng, Jason H Kurzer, Corina Schneidawind, Stephen Hon-Kit Wong, Michael C Bassik, Michael L Cleary
There is limited understanding of how signaling pathways are altered by oncogenic fusion transcription factors that drive leukemogenesis. To address this, we interrogated activated signaling pathways in a comparative analysis of mouse and human leukemias expressing the fusion protein E2A-PBX1, which is present in 5%-7% of pediatric and 50% of pre-B-cell receptor (preBCR(+)) acute lymphocytic leukemia (ALL). In this study, we describe remodeling of signaling networks by E2A-PBX1 in pre-B-ALL, which results in hyperactivation of the key oncogenic effector enzyme PLCγ2...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27751885/constitutive-activation-of-t-cells-by-%C3%AE-2-herpesviral-gpcr-through-the-interaction-with-cellular-cxcr4
#10
Eun-Kyung Kwon, Chan-Ki Min, Yuri Kim, Jae-Won Lee, Abdimadiyeva Aigerim, Sebastian Schmidt, Hyun-Jun Nam, Seong Kyu Han, Kuglae Kim, Jeong Seok Cha, Hoyoung Kim, Sanguk Kim, Hyun-Soo Cho, Myung-Sik Choi, Nam-Hyuk Cho
Members of the herpesviral family use multiple strategies to hijack infected host cells and exploit cellular signaling for their pathogenesis and latent infection. Among the most intriguing weapons in the arsenal of pathogenic herpesviruses are the constitutively active virally-encoded G protein-coupled receptors (vGPCRs). Even though vGPCRs contribute to viral pathogenesis such as immune evasion and proliferative disorders, the molecular details of how vGPCRs continuously activate cellular signaling are largely unknown...
October 15, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27742830/lck-inhibits-heat-shock-protein-65-mediated-reverse-cholesterol-transport-in-t-cells
#11
Tiantian Luo, Jing Hu, Dan Xi, Haowei Xiong, Wenshuai He, Jichen Liu, Menghao Li, Hao Lu, Jinzhen Zhao, Wenyan Lai, Zhigang Guo
Previously, we reported that heat shock protein (HSP)65 impairs the effects of high-density lipoprotein on macrophages. We also showed that immune response activation adversely affects reverse cholesterol transport (RCT). In this study, we investigated the effects of the Src family kinase lymphocyte-specific protein tyrosine kinase (Lck) and elucidated the mechanism underlying HSP65-regulated cholesterol efflux in T cells. We evaluated cell proliferation, Lck expression, and inflammatory cytokine production in Jurkat cells and CD4(+) T cells...
October 14, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27700984/an-electrostatic-selection-mechanism-controls-sequential-kinase-signaling-downstream-of-the-t-cell-receptor
#12
Neel H Shah, Qi Wang, Qingrong Yan, Deepti Karandur, Theresa A Kadlecek, Ian R Fallahee, William P Russ, Rama Ranganathan, Arthur Weiss, John Kuriyan
The sequence of events that initiates T cell signaling is dictated by the specificities and order of activation of the tyrosine kinases that signal downstream of the T cell receptor. Using a platform that combines exhaustive point-mutagenesis of peptide substrates, bacterial surface-display, cell sorting, and deep sequencing, we have defined the specificities of the first two kinases in this pathway, Lck and ZAP-70, for the T cell receptor ζ chain and the scaffold proteins LAT and SLP-76. We find that ZAP-70 selects its substrates by utilizing an electrostatic mechanism that excludes substrates with positively-charged residues and favors LAT and SLP-76 phosphosites that are surrounded by negatively-charged residues...
October 4, 2016: ELife
https://www.readbyqxmd.com/read/27681140/the-antagonism-of-hiv-1-nef-to-serinc5-particle-infectivity-restriction-involves-the-counteraction-of-virion-associated-pools-of-the-restriction-factor
#13
Birthe Trautz, Virginia Pierini, Rebecka Wombacher, Bettina Stolp, Amanda J Chase, Massimo Pizzato, Oliver T Fackler
: SERINC3 (serine incorporator 3) and SERINC5 are recently identified host cell inhibitors of HIV-1 particle infectivity that are counteracted by the viral pathogenesis factor Nef. Here we confirm that HIV-1 Nef, but not HIV-1 Vpu, antagonizes the particle infectivity restriction of SERINC5. SERINC5 antagonism occurred in parallel with other Nef activities, including cell surface receptor downregulation, trans-Golgi network targeting of Lck, and inhibition of host cell actin dynamics...
December 1, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27630246/hiv-envelope-gp120-alters-t-cell-receptor-mobilization-in-the-immunological-synapse-of-uninfected-cd4-t-cells-and-augments-t-cell-activation
#14
Jing Deng, Yu-Ya Mitsuki, Guomiao Shen, Jocelyn C Ray, Claudia Cicala, James Arthos, Michael L Dustin, Catarina E Hioe
: HIV is transmitted most efficiently from cell to cell, and productive infection occurs mainly in activated CD4 T cells. It is postulated that HIV exploits immunological synapses formed between CD4 T cells and antigen-presenting cells to facilitate the targeting and infection of activated CD4 T cells. This study sought to evaluate how the presence of the HIV envelope (Env) in the CD4 T cell immunological synapse affects synapse formation and intracellular signaling to impact the downstream T cell activation events...
December 1, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27616195/dissection-of-local-ca-2-signals-inside-cytosol-by-er-targeted-ca-2-indicator
#15
Fumihiro Niwa, Shigeo Sakuragi, Ayana Kobayashi, Shin Takagi, Yoichi Oda, Hiroko Bannai, Katsuhiko Mikoshiba
Calcium (Ca(2+)) is a versatile intracellular second messenger that operates in various signaling pathways leading to multiple biological outputs. The diversity of spatiotemporal patterns of Ca(2+) signals, generated by the coordination of Ca(2+) influx from the extracellular space and Ca(2+) release from the intracellular Ca(2+) store the endoplasmic reticulum (ER), is considered to underlie the diversity of biological outputs caused by a single signaling molecule. However, such Ca(2+) signaling diversity has not been well described because of technical limitations...
October 7, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27601584/t-cell-immune-deficiency-in-zap70-mutant-zebrafish
#16
John C Moore, Timothy S Mulligan, Nora Torres Yordán, Daniel Castranova, Van N Pham, Qin Tang, Riadh Lobbardi, Anthony Anselmo, Robert S Liwski, Jason N Berman, Ruslan I Sadreyev, Brant M Weinstein, David M Langenau
The zeta-chain (TCR) associated protein kinase 70kDa (ZAP70) is required for T-cell activation. ZAP70 deficiencies in humans and null mutations in mice lead to severe combined immunodeficiency. Here, we describe a zap70 loss-of-function mutation in zebrafish (zap70(y442)) that was created using TALENs. In contrast to what has been reported in morphant zebrafish, zap70(y442) homozygous mutant zebrafish displayed normal development of blood and lymphatic vasculature. Hematopoietic cell development was also largely unaffected in mutant larvae...
September 6, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27582389/spindle-function-in-xenopus-oocytes-involves-possible-nanodomain-calcium-signaling
#17
Ruizhen Li, Julie Leblanc, Kevin He, X Johné Liu
Intracellular calcium transients are a universal phenomenon at fertilization and are required for egg activation, but the exact role of Ca(2+) in second polar body emission remains unknown. On the other hand, similar calcium transients have not been demonstrated during oocyte maturation and, yet, manipulating intracellular calcium levels interferes with first polar body emission, in mice and frogs. To determine the precise role of calcium signaling in polar body formation, we used live cell imaging coupled with temporally precise intracellular calcium buffering...
August 31, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27582059/targeting-bcl-2-and-abl-lyn-in-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#18
Jessica T Leonard, Joelle S J Rowley, Christopher A Eide, Elie Traer, Brandon Hayes-Lattin, Marc Loriaux, Stephen E Spurgeon, Brian J Druker, Jeffrey W Tyner, Bill H Chang
Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) remains a challenge. Although the addition of targeted tyrosine kinase inhibitors (TKIs) to standard cytotoxic therapy has greatly improved upfront treatment, treatment-related morbidity and mortality remain high. TKI monotherapy provides only temporary responses and renders patients susceptible to the development of TKI resistance. Thus, identifying agents that could enhance the activity of TKIs is urgently needed. Recently, a selective inhibitor of B cell lymphoma 2 (BCL-2), ABT-199 (venetoclax), has shown impressive activity against hematologic malignancies...
August 31, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27579049/chemomics-integrated-proteomics-analysis-of-jie-geng-tang-to-ameliorate-lipopolysaccharide-induced-acute-lung-injury-in-mice
#19
Jin Tao, Yan Nie, Yuanyuan Hou, Xiaoyao Ma, Guoyu Ding, Jie Gao, Min Jiang, Gang Bai
Jie-Geng-Tang (JGT), a classic and famous traditional Chinese medicine (TCM) prescription composed of Platycodon grandiflorum (Jacq.) A. DC. (PG) and Glycyrrhiza uralensis Fisch. (GU), is well known for "clearing heat and relieving toxicity" and its ability to "diffuse the lung and relieve sore throat." However, the mechanism underlying its action remains unclear. In this study, potential anti-inflammatory ingredients were screened and submitted to PharmMapper and the KEGG bioinformatics website to predict the target proteins and related pathways, respectively...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/27571702/ameliorative-effects-of-artemisia-argyi-folium-extract-on-2-4%C3%A2-dinitrochlorobenzene%C3%A2-induced-atopic-dermatitis%C3%A2-like-lesions-in-balb-c-mice
#20
Hyoung-Min Han, Seung-Ju Kim, Jong-Sik Kim, Bum Hoi Kim, Hai Woong Lee, Yong Tae Lee, Kyung-Hwa Kang
Artemisia argyi Folium has been used to treat skin diseases, including eczema and dermatitis, in South Korean medicine. The present study investigated the curative effects of Artemisia argyi Folium extract (AAFE) on 2,4‑dinitrochlorobenzene (DNCB)‑induced atopic dermatitis (AD)‑like skin lesions in a BALB/c mouse model. Briefly, the dorsal skin of the BALB/c mice was sensitized three times with DNCB, whereas the ears were challenged twice. Repeated treatment with DNCB induced AD‑like lesions. The effects of AAFE on AD‑like lesions were evaluated by clinical observation, histopathological analysis, immunohistochemistry and enzyme‑linked immunosorbent assay...
October 2016: Molecular Medicine Reports
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