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Adaptor protein 2

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https://www.readbyqxmd.com/read/27909244/cd4-down-regulation-by-hiv-1-nef-reveals-distinct-roles-for-%C3%AE-1-and-%C3%AE-2-subunits-of-ap-1-complex-in-protein-trafficking
#1
Lucas A Tavares, Eulália M L da Silva, Mara E da Silva-Januário, Yunan C Januário, Julianne V de Cavalho, Érika S Czernisz, Gonzalo A Mardones, Luis L P daSilva
The HIV accessory protein Nef is a major determinant of viral pathogenesis that facilitates viral particle release, prevents viral antigen presentation and increases infectivity of new virus particles. These functions of Nef involve its ability to remove specific host proteins from the surface of infected cells, including the CD4 receptor. Nef binds to the adaptor protein 2 (AP-2) and CD4 in clathrin-coated pits, forcing CD4 internalization and subsequent target to lysosomes. Herein, we report that this lysosomal targeting requires a variant of the AP-1 comprising the isoform 2 of γ-adaptin...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27896837/cd6-and-linker-of-activated-t-cells-are-potential-interaction-partners-for-t-cell-specific-adaptor-protein
#2
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/27889498/bloc-2-subunit-hps6-deficiency-affects-the-tubulation-and-secretion-of-von-willebrand-factor-from-mouse-endothelial-cells
#3
Jing Ma, Zhe Zhang, Lin Yang, Janos Kriston-Vizi, Daniel F Cutler, Wei Li
Hermansky-Pudlak syndrome (HPS) is a recessive disorder with bleeding diathesis, which has been linked to platelet granule defects. Both platelet granules and endothelial Weibel-Palade bodies (WPBs) are members of lysosome-related organelles (LROs) whose formation is regulated by HPS protein associated complexes such as BLOC (biogenesis of lysosome organelles complex) -1, -2, -3, AP-3 (adaptor protein complex-3) and HOPS (homotypic fusion and protein sorting complex). Von Willebrand factor (VWF) is critical to hemostasis, which is stored in a highly-multimerized form as tubules in the WPBs...
October 21, 2016: Journal of Genetics and Genomics, Yi Chuan Xue Bao
https://www.readbyqxmd.com/read/27889060/autosomal-recessive-mutations-in-ap3b2-adaptor-related-protein-complex-3-beta-2-subunit-cause-an-early-onset-epileptic-encephalopathy-with-optic-atrophy
#4
Mirna Assoum, Christophe Philippe, Bertrand Isidor, Laurence Perrin, Periklis Makrythanasis, Neal Sondheimer, Caroline Paris, Jessica Douglas, Gaetan Lesca, Stylianos Antonarakis, Hanan Hamamy, Thibaud Jouan, Yannis Duffourd, Stéphane Auvin, Aline Saunier, Amber Begtrup, Catherine Nowak, Nicolas Chatron, Dorothée Ville, Kamiar Mireskandari, Paolo Milani, Philippe Jonveaux, Guylène Lemeur, Mathieu Milh, Masano Amamoto, Mitsuhiro Kato, Mitsuko Nakashima, Noriko Miyake, Naomichi Matsumoto, Amira Masri, Christel Thauvin-Robinet, Jean-Baptiste Rivière, Laurence Faivre, Julien Thevenon
Early-onset epileptic encephalopathy (EOEE) represents a heterogeneous group of severe disorders characterized by seizures, interictal epileptiform activity with a disorganized electroencephalography background, developmental regression or retardation, and onset before 1 year of age. Among a cohort of 57 individuals with epileptic encephalopathy, we ascertained two unrelated affected individuals with EOEE associated with developmental impairment and autosomal-recessive variants in AP3B2 by means of whole-exome sequencing...
December 1, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27876844/the-n-terminal-loop-of-irak-4-death-domain-regulates-ordered-assembly-of-the-myddosome-signalling-scaffold
#5
Anthony C G Dossang, Precious G Motshwene, Yang Yang, Martyn F Symmons, Clare E Bryant, Satty Borman, Julie George, Alexander N R Weber, Nicholas J Gay
Activation of Toll-like receptors induces dimerization and the recruitment of the death domain (DD) adaptor protein MyD88 into an oligomeric post receptor complex termed the Myddosome. The Myddosome is a hub for inflammatory and oncogenic signaling and has a hierarchical arrangement with 6-8 MyD88 molecules assembling with exactly 4 of IRAK-4 and 4 of IRAK-2. Here we show that a conserved motif in IRAK-4 (Ser8-X-X-X-Arg12) is autophosphorylated and that the phosphorylated DD is unable to form Myddosomes. Furthermore a mutant DD with the phospho-mimetic residue Asp at this position is impaired in both signalling and Myddosome assembly...
November 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27858941/block-one-unleash-a-hundred-mechanisms-of-dab2ip-inactivation-in-cancer
#6
REVIEW
Arianna Bellazzo, Giulio Di Minin, Licio Collavin
One of the most defining features of cancer is aberrant cell communication; therefore, a molecular understanding of the intricate network established among tumor cells and their microenvironment could significantly improve comprehension and clinical management of cancer. The tumor suppressor DAB2IP (Disabled homolog 2 interacting protein), also known as AIP1 (ASK1 interacting protein), has an important role in this context, as it modulates signal transduction by multiple inflammatory cytokines and growth factors...
November 18, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27854239/kshv-entry-and-trafficking-in-target-cells-hijacking-of-cell-signal-pathways-actin-and-membrane-dynamics
#7
REVIEW
Binod Kumar, Bala Chandran
Kaposi's sarcoma associated herpesvirus (KSHV) is etiologically associated with human endothelial cell hyperplastic Kaposi's sarcoma and B-cell primary effusion lymphoma. KSHV infection of adherent endothelial and fibroblast cells are used as in vitro models for infection and KSHV enters these cells by host membrane bleb and actin mediated macropinocytosis or clathrin endocytosis pathways, respectively. Infection in endothelial and fibroblast cells is initiated by the interactions between multiple viral envelope glycoproteins and cell surface associated heparan sulfate (HS), integrins (α3β1, αVβ3 and αVβ5), and EphA2 receptor tyrosine kinase (EphA2R)...
November 14, 2016: Viruses
https://www.readbyqxmd.com/read/27852822/targeted-elimination-of-g-proteins-and-arrestins-defines-their-specific-contributions-to-both-intensity-and-duration-of-g-protein-coupled-receptor-signalling
#8
Elisa Alvarez-Curto, Asuka Inoue, Laura Jenkins, Sheikh Zahir Raihan, Rudi Prihandoko, Andrew B Tobin, Graeme Milligan
G protein-coupled receptors (GPCRs) can initiate intracellular signalling cascades by coupling to an array of heterotrimeric G proteins and arrestin adaptor proteins. Understanding the contribution of each of these coupling options to GPCR signalling has been hampered by a paucity of tools to selectively perturb receptor function. Here we employ CRISPR/Cas9 genome editing to eliminate selected G proteins (Gαq and Gα11) or arrestin2 and arrestin3 from HEK293 cells, together with the elimination of receptor phosphorylation sites, to define the relative contribution of G proteins, arrestins and receptor phosphorylation to the signalling outcomes of the free fatty acid receptor 4 (FFA4)...
November 16, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27832589/the-salmonella-effector-sted-mediates-march8-dependent-ubiquitination-of-mhc-ii-molecules-and-inhibits-t-cell-activation
#9
Ethel Bayer-Santos, Charlotte H Durkin, Luciano A Rigano, Andreas Kupz, Eric Alix, Ondrej Cerny, Elliott Jennings, Mei Liu, Aindrias S Ryan, Nicolas Lapaque, Stefan H E Kaufmann, David W Holden
The SPI-2 type III secretion system (T3SS) of intracellular Salmonella enterica translocates effector proteins into mammalian cells. Infection of antigen-presenting cells results in SPI-2 T3SS-dependent ubiquitination and reduction of surface-localized mature MHC class II (mMHCII). We identify the effector SteD as required and sufficient for this process. In Mel Juso cells, SteD localized to the Golgi network and vesicles containing the E3 ubiquitin ligase MARCH8 and mMHCII. SteD caused MARCH8-dependent ubiquitination and depletion of surface mMHCII...
November 9, 2016: Cell Host & Microbe
https://www.readbyqxmd.com/read/27820851/appl1-mediating-leptin-signaling-contributes-to-proliferation-and-migration-of-cancer-cells
#10
Youming Ding, Yingkang Cao, Bin Wang, Lei Wang, Yemin Zhang, Deling Zhang, Xiaoyan Chen, Mingxin Li, Changhua Wang
Leptin has been implicated in tumorigenesis and tumor progression, particularly in obese patients. As a multifunctional adaptor protein, APPL1 (containing pleckstrin homology domain, phosphotyrosine binding domain, and a leucine zipper motif 1) plays a critical role in regulating adiponectin and insulin signaling pathways. Currently, high APPL1 level has been suggested to be related to metastases and progression of some types of cancer. However, the intercourse between leptin signaling pathway and APPL1 remains poorly understood...
2016: PloS One
https://www.readbyqxmd.com/read/27819682/ripk1-inhibits-zbp1-driven-necroptosis-during-development
#11
Kim Newton, Katherine E Wickliffe, Allie Maltzman, Debra L Dugger, Andreas Strasser, Victoria C Pham, Jennie R Lill, Merone Roose-Girma, Søren Warming, Margaret Solon, Hai Ngu, Joshua D Webster, Vishva M Dixit
Receptor-interacting protein kinase 1 (RIPK1) promotes cell survival-mice lacking RIPK1 die perinatally, exhibiting aberrant caspase-8-dependent apoptosis and mixed lineage kinase-like (MLKL)-dependent necroptosis. However, mice expressing catalytically inactive RIPK1 are viable, and an ill-defined pro-survival function for the RIPK1 scaffold has therefore been proposed. Here we show that the RIP homotypic interaction motif (RHIM) in RIPK1 prevents the RHIM-containing adaptor protein ZBP1 (Z-DNA binding protein 1; also known as DAI or DLM1) from activating RIPK3 upstream of MLKL...
December 1, 2016: Nature
https://www.readbyqxmd.com/read/27813252/the-calcium-binding-protein-alg-2-promotes-er-exit-site-localization-and-polymerization-of-tfg
#12
Takashi Kanadome, Hideki Shibata, Keiko Kuwata, Terunao Takahara, Masatoshi Maki
ALG-2 (apoptosis-linked gene 2, a gene product of PDCD6) is a 22-kDa Ca(2+) -binding protein. Accumulating evidence points to a role for ALG-2 as a Ca(2+) -responsive adaptor protein. On binding to Ca(2+) , ALG-2 undergoes a conformational change that facilitates its interaction with various proteins. It also forms a homodimer and heterodimer with peflin, a paralog of ALG-2. However, the differences in cellular roles for the ALG-2 homodimer and ALG-2/peflin heterodimer are unclear. Here, we found that TFG (Trk-fused gene) interacted with the ALG-2 homodimer...
November 4, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27813071/what-goes-up-must-come-down-a-tripartite-dok-3-grb2-ship1-inhibitory-module-limits-bcr-signaling
#13
Michael Reth, Michael R Gold
Properly regulated immunity requires precise integration of activating and inhibitory signals. As for other lymphocytes, B cells express an antigen-specific activating receptor, the B-cell antigen receptor (BCR), and inhibitory receptors (e.g. FcγRIIb) that exercise checkpoint control on B-cell activation. Moreover, following BCR engagement, CD19 recruits proteins that amplify BCR signaling, while CD22 initiates a negative feedback loop by recruiting proteins that inhibit BCR signaling. Initial BCR signaling is mediated by protein tyrosine kinases and lipid kinases; inhibitory receptors directly antagonize the actions of these enzymes by recruiting protein tyrosine phosphatases and lipid phosphatases and positioning them close to actively signaling BCRs...
November 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27807832/transcriptome-and-proteome-analyses-of-tnfaip8-knockdown-cancer-cells-reveal-new-insights-into-molecular-determinants-of-cell-survival-and-tumor-progression
#14
Timothy F Day, Rajshree R Mewani, Joshua Starr, Xin Li, Debyani Chakravarty, Habtom Ressom, Xiaojun Zou, Ofer Eidelman, Harvey B Pollard, Meera Srivastava, Usha N Kasid
Tumor necrosis factor-α-inducible protein 8 (TNFAIP8) is the first discovered oncogenic and an anti-apoptotic member of a conserved TNFAIP8 or TIPE family of proteins. TNFAIP8 mRNA is induced by NF-kB, and overexpression of TNFAIP8 has been correlated with poor prognosis in many cancers. Downregulation of TNFAIP8 expression has been associated with decreased pulmonary colonization of human tumor cells, and enhanced sensitivities of tumor xenografts to radiation and docetaxel. Here we have investigated the effects of depletion of TNFAIP8 on the mRNA, microRNA and protein expression profiles in prostate and breast cancers and melanoma...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27807399/electric-stimulation-of-the-vagus-nerve-reduced-mouse-neuroinflammation-induced-by-lipopolysaccharide
#15
G Meneses, M Bautista, A Florentino, G Díaz, G Acero, H Besedovsky, D Meneses, A Fleury, A Del Rey, G Gevorkian, G Fragoso, E Sciutto
BACKGROUND: Neuroinflammation (NI) is a key feature in the pathogenesis and progression of infectious and non-infectious neuropathologies, and its amelioration usually improves the patient outcome. Peripheral inflammation may promote NI through microglia and astrocytes activation, an increased expression of inflammatory mediators and vascular permeability that may lead to neurodegeneration. Several anti-inflammatory strategies have been proposed to control peripheral inflammation. Among them, electrical stimulation of the vagus nerve (VNS) recently emerged as an alternative to effectively attenuate peripheral inflammation in a variety of pathological conditions with few side effects...
2016: Journal of Inflammation
https://www.readbyqxmd.com/read/27803322/s2-from-equine-infectious-anemia-virus-is-an-infectivity-factor-which-counteracts-the-retroviral-inhibitors-serinc5-and-serinc3
#16
Ajit Chande, Emilia Cristiana Cuccurullo, Annachiara Rosa, Serena Ziglio, Susan Carpenter, Massimo Pizzato
The lentivirus equine infectious anemia virus (EIAV) encodes the small protein S2, a pathogenic determinant that is important for virus replication and disease progression in horses. No molecular function had been linked to this accessory protein. We report that S2 can replace the activity of Negative factor (Nef) in HIV-1 infectivity, being required to antagonize the inhibitory activity of Serine incorporator (SERINC) proteins on Nef-defective HIV-1. Like Nef, S2 excludes SERINC5 from virus particles and requires an ExxxLL motif predicted to recruit the clathrin adaptor, Adaptor protein 2 (AP2)...
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27802184/the-role-of-tks-adaptor-proteins-in-invadopodia-formation-growth-and-metastasis-of-melanoma
#17
Shinji Iizuka, Christopher Abdullah, Matthew D Buschman, Begoña Diaz, Sara A Courtneidge
Metastatic cancer cells are characterized by their ability to degrade and invade through extracellular matrix. We previously showed that the Tks adaptor proteins, Tks4 and Tks5, are required for invadopodia formation and/or function in Src-transformed fibroblasts and a number of human cancer cell types. In this study, we investigated the role of Tks adaptor proteins in melanoma cell invasion and metastasis. Knockdown of either Tks4 or Tks5 in both mouse and human melanoma cell lines resulted in a decreased ability to form invadopodia and degrade extracellular matrix...
October 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27799303/different-doublecortin-dcx-patient-alleles-show-distinct-phenotypes-in-cultured-neurons-evidence-for-divergent-loss-of-function-and-off-pathway-cellular-mechanisms
#18
Chan Choo Yap, Laura Digilio, Lloyd McMahon, Matylda Roszkowska, Christopher J Bott, Kamil Kruczek, Bettina Winckler
DCX (doublecortin on the X-chromosome) is a neuronal microtubule-binding protein with a multitude of roles in neurodevelopment. In humans, DCX is a major genetic locus for X-linked lissencephaly. The best-studied defects are in neuronal migration during corticogenesis and in the hippocampus, as well as axon and dendrite growth defects. Much effort has been directed at understanding the molecular and cellular bases of DCX-linked lissencephaly. The focus has been in particular on defects in microtubule assembly and bundling, using knock-out mice and expression of WT and mutant DCX in non-neuronal cells...
October 31, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27798240/identification-of-the-endocytic-sorting-signal-recognized-by-the-art1-rsp5-ubiquitin-ligase-complex
#19
Evan L Guiney, Till Klecker, Scott D Emr
Targeted endocytosis of plasma membrane (PM) proteins allows cells to adjust their complement of membrane proteins to changing extracellular conditions. For a wide variety of PM proteins, initiation of endocytosis is triggered by ubiquitination. In yeast, Arrestin-Related Trafficking adaptors (ARTs) enable a single ubiquitin ligase, Rsp5, to specifically and selectively target a wide range of PM proteins for ubiquitination and endocytosis. However, the mechanisms that allow ARTs to specifically recognize their appropriate substrates are unknown...
October 19, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27791135/crystal-structure-of-the-cohesin-loader-scc2-and-insight-into-cohesinopathy
#20
Sotaro Kikuchi, Dominika M Borek, Zbyszek Otwinowski, Diana R Tomchick, Hongtao Yu
The ring-shaped cohesin complex topologically entraps chromosomes and regulates chromosome segregation, transcription, and DNA repair. The cohesin core consists of the structural maintenance of chromosomes 1 and 3 (Smc1-Smc3) heterodimeric ATPase, the kleisin subunit sister chromatid cohesion 1 (Scc1) that links the two ATPase heads, and the Scc1-bound adaptor protein Scc3. The sister chromatid cohesion 2 and 4 (Scc2-Scc4) complex loads cohesin onto chromosomes. Mutations of cohesin and its regulators, including Scc2, cause human developmental diseases termed cohesinopathy...
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
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