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Adaptor protein 2

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https://www.readbyqxmd.com/read/28430604/signal-transducing-adaptor-protein-2-promotes-generation-of-functional-long-term-memory-cd8-t-cells-by-preventing-terminal-effector-differentiation
#1
Daisuke Muraoka, Naohiro Seo, Tae Hayashi, Chisaki Hyuga-Amaike, Kana Okamori, Isao Tawara, Naozumi Harada, Hiroshi Shiku
Long-surviving memory CD8+ T cells generated by stimulation with appropriate tumor-associated antigens are the most aggressive and persistent tumoricidal effectors. In this event of memory CD8+ T cell development, the signal transducer and activator of transcription (STAT) proteins function as the crucial intracellular signaling molecules, but the regulatory mechanism of STATs in CD8+ T cells is not fully understood. In this study, we report for the first time, by using murine vaccination models, that signal-transducing adaptor protein-2 (STAP2) maintains the cytotoxicity of long-lived memory CD8+ T cells by controlling a STAT3/suppressor of cytokine signaling 3 (SOCS3) cascade...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416805/a-new-inhibitor-of-the-%C3%AE-arrestin-ap2-endocytic-complex-reveals-interplay-between-gpcr-internalization-and-signalling
#2
Alexandre Beautrait, Justine S Paradis, Brandon Zimmerman, Jenna Giubilaro, Ljiljana Nikolajev, Sylvain Armando, Hiroyuki Kobayashi, Lama Yamani, Yoon Namkung, Franziska M Heydenreich, Etienne Khoury, Martin Audet, Philippe P Roux, Dmitry B Veprintsev, Stéphane A Laporte, Michel Bouvier
In addition to G protein-coupled receptor (GPCR) desensitization and endocytosis, β-arrestin recruitment to ligand-stimulated GPCRs promotes non-canonical signalling cascades. Distinguishing the respective contributions of β-arrestin recruitment to the receptor and β-arrestin-promoted endocytosis in propagating receptor signalling has been limited by the lack of selective analytical tools. Here, using a combination of virtual screening and cell-based assays, we have identified a small molecule that selectively inhibits the interaction between β-arrestin and the β2-adaptin subunit of the clathrin adaptor protein AP2 without interfering with the formation of receptor/β-arrestin complexes...
April 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28388438/lsm12-and-me31b-ddx6-define-distinct-modes-of-posttranscriptional-regulation-by-ataxin-2-protein-complex-in-drosophila-circadian-pacemaker-neurons
#3
Jongbo Lee, Eunseok Yoo, Hoyeon Lee, Keunhee Park, Jin-Hoe Hur, Chunghun Lim
ATAXIN-2 (ATX2) has been implicated in human neurodegenerative diseases, yet it remains elusive how ATX2 assembles specific protein complexes to execute its physiological roles. Here we employ the posttranscriptional co-activator function of Drosophila ATX2 to demonstrate that LSM12 and ME31B/DDX6 are two ATX2-associating factors crucial for sustaining circadian rhythms. LSM12 acts as a molecular adaptor for the recruitment of TWENTY-FOUR (TYF) to ATX2. The ATX2-LSM12-TYF complex thereby stimulates TYF-dependent translation of the rate-limiting clock gene period (per) to maintain 24 hr periodicity in circadian behaviors...
April 6, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28387218/retrograde-transport-of-trkb-containing-autophagosomes-via-the-adaptor-ap-2-mediates-neuronal-complexity-and-prevents-neurodegeneration
#4
Natalia L Kononenko, Gala A Claßen, Marijn Kuijpers, Dmytro Puchkov, Tanja Maritzen, Aleksandra Tempes, Anna R Malik, Agnieszka Skalecka, Sujoy Bera, Jacek Jaworski, Volker Haucke
Autophagosomes primarily mediate turnover of cytoplasmic proteins or organelles to provide nutrients and eliminate damaged proteins. In neurons, autophagosomes form in distal axons and are trafficked retrogradely to fuse with lysosomes in the soma. Although defective neuronal autophagy is associated with neurodegeneration, the function of neuronal autophagosomes remains incompletely understood. We show that in neurons, autophagosomes promote neuronal complexity and prevent neurodegeneration in vivo via retrograde transport of brain-derived neurotrophic factor (BDNF)-activated TrkB receptors...
April 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28384159/3lps-binding-protein-and-its-interactions-with-p-gingivalis-lps-modulate-pro-inflammatory-response-and-toll-like-receptor-signaling-in-human-oral-keratinocytes
#5
Pei-Hui Ding, Richard P Darveau, Cun-Yu Wang, Lijian Jin
Lipopolysaccharide (LPS)-binding protein (LBP) as an acute-phase protein plays a crucial role in innate host response to bacterial challenge. Our previous study shows that LBP expression in human gingiva is associated with periodontal status. Porphyromonas gingivalis is a keystone periodontopathogen, and its LPS with lipid A structural heterogeneity critically accounts for periodontal pathogenesis. This study investigated the effects of LBP and its interactions with two featured isoforms of P. gingivalis LPS (tetra-acylated LPS1435/1449 and penta-acylated LPS1690) on the expression of pro-inflammatory cytokines in human oral keratinocytes (HOKs), and the involvement of Toll-like receptor (TLR) signaling...
2017: PloS One
https://www.readbyqxmd.com/read/28381191/expression-and-associations-of-traf1-bmi-1-aldh1-and-lin28b-in-oral-squamous-cell-carcinoma
#6
Tian-Fu Wu, Yi-Cun Li, Si-Rui Ma, Bing-Liu, Wen-Feng Zhang, Zhi-Jun Sun
Tumor necrosis factor receptor-associated factor 1, an adaptor protein of tumor necrosis factor 2, is involved in classical nuclear factor (NF)-κB activation and lymphocyte recruitment. However, less is known about the expression and association of tumor necrosis factor receptor-associated factor 1 with cancer stem cell markers in oral squamous cell carcinoma. This study aimed to investigate the expression of tumor necrosis factor receptor-associated factor 1 and stem cell characteristic markers (lin28 homolog B, B cell-specific Moloney murine leukemia virus integration site 1, and aldehyde dehydrogenase 1) in oral squamous cell carcinoma and analyze their relations...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28377308/cell-type-specific-regulatory-effects-of-glucocorticoids-on-cutaneous-tlr2-expression-and-signalling
#7
Qi Su, Anja Pfalzgraff, Günther Weindl
Glucocorticoids (GCs) induce Toll-like receptor (TLR) 2 expression and synergistically upregulate TLR2 with pro-inflammatory cytokines or bacteria. These paradoxical effects have drawn attention to the inflammatory initiating or promoting effects of GCs, as GC treatment can provoke inflammatory skin diseases. Here, we aimed to investigate the regulatory effects of GCs in human skin cells of different epidermal and dermal layers. We found that Dex induced TLR2 expression mainly in undifferentiated and less in calcium-induced differentiated keratinocytes but not in HaCaT cells or fibroblasts, however, Dex reduced TLR1/6 expression...
April 1, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28375585/down-regulation-of-talin1-promotes-hepatocellular-carcinoma-progression-via-activation-of-the-erk1-2-pathway
#8
Chen Peijuan, Lei Ling, Wang Jian, Zou Xuejing, Zhang Dongyan, Deng Ling, Wu Dehua
Talin1 is an adaptor protein that conjugates integrins to the cytoskeleton and regulates integrins and focal adhesion signaling. Several studies have found that Talin1 is over-expressed in several tumor types and promotes tumor progression. However, the explicit role of Talin1 in hepatocellular carcinoma (HCC) progression is still unclear and its functional mechanism remains largely unknown. In this study, we showed a trend of gradually decreasing expression of Talin1 from normal liver tissues to hepatocirrhosis, liver hyperplasia, the corresponding adjacent non-tumor, primary HCC and eventually metastatic foci, indicating that Talin1 maybe correlate with HCC initiation to progression...
April 4, 2017: Cancer Science
https://www.readbyqxmd.com/read/28370480/pop1-might-be-recruiting-its-type-ia-interface-for-nlrp3-mediated-pyd-pyd-interaction-insights-from-md-simulation
#9
Jitendra Maharana, Ashutosh Vats, Santwana Gautam, Bibhu Prasad Nayak, Sushil Kumar, Jasobanta Sendha, Sachinandan De
Inflammasomes are multiprotein caspase-activating complexes that enhance the maturation and release of proinflammatory cytokines (IL-1β and IL-18) in response to the invading pathogen and/or host-derived cellular stress. These are assembled by the sensory proteins (viz NLRC4, NLRP1, NLRP3, and AIM-2), adaptor protein (ASC), and effector molecule procaspase-1. In NLRP3-mediated inflammasome activation, ASC acts as a mediator between NLRP3 and procaspase-1 for the transmission of signals. A series of homotypic protein-protein interactions (NLRP3(PYD) :ASC(PYD) and ASC(CARD) :CASP1(CARD) ) propagates the downstream signaling for the production of proinflammatory cytokines...
April 3, 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/28363496/therapeutic-progenitor-cell-application-for-tissue-regeneration-analyzing-the-impact-of-toll-like-receptor-signaling-on-c-kit-cell-migration-following-ischemia-reperfusion-injury-in-vivo
#10
Peter Donndorf, Saifullah Abubaker, Brigitte Vollmar, Christian Rimmbach, Gustav Steinhoff, Alexander Kaminski
OBJECTIVES: Toll-like-receptor (TLR) mediated immune response has been shown to regulate myocardial damage following cardiac ischemia-reperfusion (IR). It has not been described conclusively so far whether migration of therapeutically applied progenitor cells following an IR event depends on TLR-signaling. METHODS: In vivo migratory capacity murine c-kit(+) cells following IR injury was quantified by intravital fluorescence microscopy, utilizing the mouse cremaster muscle model and analyzing early (rolling) and late (adhesion) c-kit(+) cell interaction with the local endothelium...
March 29, 2017: Microvascular Research
https://www.readbyqxmd.com/read/28361043/cleavage-of-grb2-associated-binding-protein-2-by-viral-proteinase-2a-during-coxsackievirus-infection
#11
Haoyu Deng, Gabriel Fung, Ye Qiu, Chen Wang, Jingchun Zhang, Zheng-Gen Jin, Honglin Luo
Coxsackievirus type B3 (CV-B3), an enterovirus associated with the pathogenesis of several human diseases, subverts, or employs the host intracellular signaling pathways to support effective viral infection. We have previously demonstrated that Grb2-associated binding protein 1 (GAB1), a signaling adaptor protein that serves as a platform for intracellular signaling assembly and transduction, is cleaved upon CV-B3 infection, resulting in a gain-of-pro-viral-function via the modification of GAB1-mediated ERK1/2 pathway...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28359760/effect-of-p62-sqstm1-polyubiquitination-on-its-autophagic-adaptor-function-and-cellular-survival-under-oxidative-stress-induced-by-arsenite
#12
Hyuna Lee, Mi-Nam Kim, Kwon-Yul Ryu
Oxidative stress induced by arsenite [As(III)] affects protein folding and results in increased levels of misfolded proteins or protein aggregates. Accumulation of misfolded protein aggregates may act as a cue signal for the oligomerization of the autophagic adaptor protein p62, which facilitates recognition of misfolded protein aggregates that are polyubiquitinated with K63 linkages. However, as the autophagic flux is impaired under exposure to As(III), p62 oligomers cannot be cleared by autophagy and accumulate as aggregates with Keap1...
March 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28348516/molecular-mechanisms-for-the-coupling-of-endocytosis-to-exocytosis-in-neurons
#13
REVIEW
Zhenli Xie, Jiangang Long, Jiankang Liu, Zuying Chai, Xinjiang Kang, Changhe Wang
Neuronal communication and brain function mainly depend on the fundamental biological events of neurotransmission, including the exocytosis of presynaptic vesicles (SVs) for neurotransmitter release and the subsequent endocytosis for SV retrieval. Neurotransmitters are released through the Ca(2+)- and SNARE-dependent fusion of SVs with the presynaptic plasma membrane. Following exocytosis, endocytosis occurs immediately to retrieve SV membrane and fusion machinery for local recycling and thus maintain the homeostasis of synaptic structure and sustained neurotransmission...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28337828/tradd-traf2-rip1-and-tak1-are-required-for-tnf-%C3%AE-induced-pro-labour-mediators-in-human-primary-myometrial-cells
#14
Ratana Lim, Gillian Barker, Martha Lappas
PROBLEM: TNF-α plays a central role in the processes of human labour and delivery. This study sought to determine the role of the adaptor proteins TNFR1-associated death domain protein (TRADD), TNF receptor-associated factor 2 (TRAF2), receptor interacting protein 1 (RIP1) and transforming growth factor beta-activated kinase 1 (TAK1) in TNF-α-induced formation of pro-labour mediators. METHOD OF STUDY: Human primary myometrial cells were transfected with siRNA against TRADD (siTRADD), TRAF2 (siTRAF2), RIP1 (siRIP1) or TAK1 (siTAK1), treated with TNF-α, and assayed for pro-inflammatory mediators expression...
March 24, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28336828/-disorders-caused-by-mutations-in-calcium-sensing-receptor-and-related-diseases
#15
Toshimi Michigami
Sensing of extracellular calcium(Ca2+)levels involves the Ca-sensing receptor(CaSR), its downstream signaling molecule Gα11, and the adaptor-related protein complex 2(AP2)that plays a role in clathrin-dependent endocytosis of CaSR. Inactivating mutations in CaSR cause familial hypocalciuric hypercalcemia type 1(FHH1)and neonatal severe hyperparathyroidism(NSHPT), while activating mutations lead to autosomal dominant hypocalcemia type 1(ADH1)and Bartter syndrome type Ⅴ. Recent studies have identified that inactivating mutations in Gα11 and σ-subunit of AP2(AP2σ)also cause FHH, and these conditions have been classified as FHH2 and FHH3, respectively...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28321204/a-comprehensive-view-of-the-%C3%AE-arrestinome
#16
Pascale Crépieux, Anne Poupon, Nathalie Langonné-Gallay, Eric Reiter, Javier Delgado, Martin H Schaefer, Thomas Bourquard, Luis Serrano, Christina Kiel
G protein-coupled receptors (GPCRs) are membrane receptors critically involved in sensing the environment and orchestrating physiological processes. As such, they transduce extracellular signals such as hormone, neurotransmitters, ions, and light into an integrated cell response. The intracellular trafficking, internalization, and signaling ability of ligand-activated GPCRs are controlled by arrestins, adaptor proteins that they interact with upon ligand binding. β-arrestins 1 and 2 in particular are now considered as hub proteins assembling multiprotein complexes to regulate receptor fate and transduce diversified cell responses...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28318976/assembly-of-cns-nodes-of-ranvier-in-myelinated-nerves-is-promoted-by-the-axon-cytoskeleton
#17
Veronica Brivio, Catherine Faivre-Sarrailh, Elior Peles, Diane L Sherman, Peter J Brophy
Nodes of Ranvier in the axons of myelinated neurons are exemplars of the specialized cell surface domains typical of polarized cells. They are rich in voltage-gated sodium channels (Nav) and thus underpin rapid nerve impulse conduction in the vertebrate nervous system [1]. Although nodal proteins cluster in response to myelination, how myelin-forming glia influence nodal assembly is poorly understood. An axoglial adhesion complex comprising glial Neurofascin155 and axonal Caspr/Contactin flanks mature nodes [2]...
April 3, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28316375/torilin-inhibits-inflammation-by-limiting-tak1-mediated-map-kinase-and-nf-%C3%AE%C2%BAb-activation
#18
Mehari Endale, Tae-Hwan Kim, Yi-Seong Kwak, Na-Mi Kim, Seung-Hyung Kim, Jae Youl Cho, Bong-Sik Yun, Man-Hee Rhee
Torilin, a sesquiterpene isolated from the fruits of Torilis japonica, has shown antimicrobial, anticancer, and anti-inflammatory properties. However, data on the mechanism of torilin action against inflammation is limited. This study aimed at determining the anti-inflammatory property of torilin in LPS-induced inflammation using in vitro model of inflammation. We examined torilin's effect on expression levels of inflammatory mediators and cytokines in LPS-stimulated RAW 264.7 macrophages. The involvement of NF-kB and AP-1, MAP kinases, and adaptor proteins were assessed...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28315351/-3-h-bmt-046091-a-potent-and-selective-radioligand-to-determine-aak1-distribution-and-target-engagement
#19
Justin V Louis, Yifeng Lu, Rick Pieschl, Yung Tian, Yang Hong, Kumaran Dandapani, Sreenivasulu Naidu, Reeba K Vikramadithyan, Carolyn Dzierba, Sarat Kumar Sarvasiddhi, Susheel J Nara, Joanne Bronson, John E Macor, Charlie Albright, Walter Kostich, Yu-Wen Li
Adaptor-associated kinase 1 (AAK1), a member of the Ark1/Prk1 family of serine/threonine kinases, plays a role in modulating clatherin coated endocytosis of specific surface receptors. We have demonstrated that AAK1 inhibitors are efficacious in rodent models of neuropathic pain (Kostich et al., 2016). Here we have characterized the binding properties and distribution pattern of the tritiated AAK1 radioligand, [(3)H]BMT-046091, in rodents and cynomolgus monkeys, and used the radioligand to measure the brain target occupancy following systemic administration of AAK1 inhibitors...
March 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28299574/physiological-and-pathological-roles-of-15-deoxy-%C3%AE-12-14-prostaglandin-j2-in-the-central-nervous-system-and-neurological-diseases
#20
REVIEW
Tatsurou Yagami, Yasuhiro Yamamoto, Hiromi Koma
Prostaglandins (PGs) are divided into conventional PGs, e.g., PGD2, and cyclopentenone-type PGs, e.g., 15-deoxy-Δ(12,14) prostaglandin J2 (15d-PGJ2). PGD2 is non-enzymatically metabolized to PGJ2, Δ(12)-PGJ2, and 15d-PGJ2. In the central nervous system, 15d-PGJ2 differentiates embryonic midbrain cells into dopaminergic neuronal cells via its nuclear peroxysome proliferator-activated receptor-γ (PPARγ). 15d-PGJ2 exerts conflict actions: proinflammatory and anti-inflammatory activities. In the brain, 15d-PGJ2 possesses opposite functions as a neuroprotectant at low concentrations and a neurotoxicant at high concentrations in the brain...
March 16, 2017: Molecular Neurobiology
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