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Adaptor protein 2

Fei Xiao, Stanley Wang, Rina Barouch-Bentov, Gregory Neveu, Szuyuan Pu, Melanie Beer, Stanford Schor, Sathish Kumar, Vlad Nicolaescu, Brett D Lindenbach, Glenn Randall, Shirit Einav
Hepatitis C virus (HCV) spreads via secreted cell-free particles or direct cell-to-cell transmission. Yet, virus-host determinants governing differential intracellular trafficking of cell-free- and cell-to-cell-transmitted virus remain unknown. The host adaptor proteins (APs) AP-1A, AP-1B, and AP-4 traffic in post-Golgi compartments, and the latter two are implicated in basolateral sorting. We reported that AP-1A mediates HCV trafficking during release, whereas the endocytic adaptor AP-2 mediates entry and assembly...
March 13, 2018: MBio
Masafumi Taniwaki, Mihoko Yoshida, Yosuke Matsumoto, Kazuho Shimura, Junya Kuroda, Hiroto Kaneko
Elotuzumab, targeting signaling lymphocytic activation molecule family 7 (SLAMF7), has been approved in combination with lenalidomide and dexamethasone (ELd) for relapsed/refractory multiple myeloma (MM) based on the findings of the phase III randomized trial ELOQUENT-2 (NCT01239797). Four-year follow-up analyses of ELOQUENT-2 have demonstrated that progression-free survival was 21% in ELd versus 14% in Ld. Elotuzumab binds a unique epitope on the membrane IgC2 domain of SLAMF7, exhibiting a dual mechanism of action: natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) and enhancement of NK cell activity...
2018: Mediterranean Journal of Hematology and Infectious Diseases
Akshay Bareja, Conrad P Hodgkinson, Erik Soderblom, Greg Waitt, Victor J Dzau
The insulin-like growth factor 1 receptor (IGF1R) is a receptor tyrosine kinase with critical roles in various biological processes. Recent results from clinical trials targeting IGF1R indicate that IGF1R signaling pathways are more complex than previously thought. Moreover, it has become increasingly clear that the function of many proteins can be understood only in the context of a network of interactions. To that end, we sought to profile IGF1R-protein interactions with the proximity-labeling technique BioID...
March 12, 2018: Journal of Biological Chemistry
Tryphena Adams, Nana Aba A Ennuson, Neils B Quashie, Godfred Futagbi, Sena Matrevi, Oheneba C K Hagan, Benjamin Abuaku, Kwadwo A Koram, Nancy O Duah
BACKGROUND: Plasmodium falciparum delayed clearance with the use of artemisinin-based combination therapy (ACTs) has been reported in some African countries. Single nucleotide polymorphisms (SNPs) in two genes, P. falciparum adaptor protein complex 2 mu subunit (pfap2mu) and ubiquitin specific protease 1 (pfubp1), have been linked to delayed clearance with ACT use in Kenya and recurrent imported malaria in Britain. With over 12 years of ACT use in Ghana, this study investigated the prevalence of SNPs in the pfap2mu and pfubp1 in Ghanaian clinical P...
March 12, 2018: Parasites & Vectors
Lilian A Martinez Carrera, Elke Gabriel, Colin Donohoe, Irmgard Hölker, Aruljothi Mariappan, Markus Storbeck, Mirka Uhlirova, Jay Gopalakrishnan, Brunhilde Wirth
BICD2 encodes a highly conserved motor adaptor protein that regulates the dynein-dynactin complex in different cellular processes. Heterozygous mutations in BICD2 cause autosomal dominant lower extremity-predominant spinal muscular atrophy-2 (SMALED2). Although, various BICD2 mutations have been shown to alter interactions with different binding partners or the integrity of the Golgi apparatus, the specific pathological effects of BICD2 mutations underlying SMALED2 remain elusive. Here, we show that the fibroblasts derived from individuals with SMALED2 exhibit stable microtubules...
March 8, 2018: Human Molecular Genetics
Kanika Vanshylla, Caren Bartsch, Christoffer Hitzing, Laura Krümpelmann, Jürgen Wienands, Niklas Engels
The B cell antigen receptor (BCR) employs enzymatically inactive adaptor proteins to facilitate activation of intracellular signaling pathways. In animal model systems, adaptor proteins of the growth factor receptor-bound 2 (Grb2) family have been shown to serve critical functions in lymphocytes. However, the roles of Grb2 and the Grb2-related adaptor protein (GRAP) in human B lymphocytes remain unclear. Using TALEN-mediated gene targeting, we show that in human B cells Grb2 and GRAP amplify signaling by the immunoglobulin tail tyrosine (ITT) motif of mIgE-containing BCRs and furthermore connect immunoreceptor tyrosine-based activation motif (ITAM) signaling to activation of the Ras-controlled Erk MAP kinase pathway...
March 9, 2018: Scientific Reports
Ke Li, Ting-Ting Zhang, Feng Wang, Bing Cui, Chen-Xi Zhao, Jiao-Jiao Yu, Xiao-Xi Lv, Xiao-Wei Zhang, Zhao-Na Yang, Bo Huang, Xia Li, Fang Hua, Zhuo-Wei Hu
Metformin has beneficial effects of preventing and treating cancers on type 2 diabetic patients. However, the role of metformin in non-diabetic cancer patients and the precise molecular mechanisms against cancer have not yet been sufficiently elucidated. We recently reported that the pseudokinase protein TRIB3 acts as a stress sensor linking metabolic stressors to cancer promotion by inhibiting autophagy and ubiquitin-proteasomal degradation systems; genetically abrogating of TRIB3 expression reduces tumourigenesis and cancer progression...
March 9, 2018: Oncogene
Ah-Yeon Kim, Hyun-Jin Shim, Hyeon-Myeong Shin, Yoo Jung Lee, Hyeonjeong Nam, Su Yeon Kim, Hyung-Sun Youn
Toll-like receptors (TLRs) play a crucial role in danger recognition and induction of innate immune response against bacterial and viral infections. The TLR adaptor molecule, toll-interleukin-1 receptor domain-containing adapter inducing interferon-β (TRIF), facilitates TLR3 and TLR4 signaling, leading to the activation of the transcription factor, NF-κB and interferon regulatory factor 3 (IRF3). Andrographolide, the active component of Andrographis paniculata, exerts anti-inflammatory effects; however, the principal molecular mechanisms remain unclear...
March 1, 2018: International Immunopharmacology
Maciek Adamowski, Madhumitha Narasimhan, Urszula Kania, Matouš Glanc, Geert De Jaeger, Jiří Friml
Clathrin-mediated endocytosis (CME) is a cellular trafficking process in which cargoes and lipids are internalized from the plasma membrane into vesicles coated with clathrin and adaptor proteins. CME is essential for many developmental and physiological processes in plants, but its underlying mechanism is not well characterised compared to that in yeast and animal systems. Here, we searched for new factors involved in CME in Arabidopsis thaliana by performing Tandem Affinity Purification of proteins that interact with clathrin light chain, a principal component of the clathrin coat...
March 6, 2018: Plant Cell
Huiling Zhu, Haibo Wang, Shuhui Wang, Zhixiao Tu, Lin Zhang, Xiuying Wang, Yongqing Hou, Chunwei Wang, Jie Chen, Yulan Liu
SCOPE: Flaxseed oil is a rich source of α-linolenic acid (ALA), which is the precursor of the long-chain n-3 polyunsaturated fatty acids (PUFAs) including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). This study investigated the protective effect of flaxseed oil against intestinal injury induced by lipopolysaccharide (LPS). MATERIALS AND RESULTS: Twenty-four weaned pigs were used in a 2 × 2 factorial experiment with dietary treatment (5% corn oil vs...
March 6, 2018: Molecular Nutrition & Food Research
Leo E Wong, Joachim Maier, Jürgen Wienands, Stefan Becker, Christian Griesinger
Proline is prevalent in intrinsically disordered proteins (IDPs). NMR assignment of proline-rich IDPs is a challenge due to low dispersion of chemical shifts. We propose here new sensitivity-enhanced 4D NMR experiments that correlate two pairs of amide resonances that are either consecutive (NHi-1 , NHi ) or flanking a proline at position i-1 (NHi-2 , NHi ). The maximum two-fold enhancement of sensitivity is achieved by employing two coherence order-selective (COS) transfers incorporated unconventionally into the pulse sequence...
February 28, 2018: Journal of the American Chemical Society
Amanda K Galan-Davila, Jiyoon Ryu, Kun Dong, Yang Xiao, Zhe Dai, Deling Zhang, Zhi Li, Amanda M Dick, Kevin D Liu, Amrita Kamat, Min Lu, Qunfeng Dong, Feng Liu, Lily Q Dong
Adiponectin is an adipocyte-derived hormone with antidiabetic activities, which include increasing the sensitivity of cells to insulin. Adaptor protein containing pleckstrin homology domain, phosphotyrosine-binding domain, and leucine zipper motif (APPL1) stimulates adiponectin signaling and promotes adiponectin's insulin-sensitizing effects by binding to two adiponectin receptors, AdipoR1 and AdipoR2, and the insulin receptor. In the present study, we report on an alternative splicing variant of APPL1 (APPL1sv) that is highly expressed in mouse liver, pancreas, and spleen tissues...
February 26, 2018: Journal of Biological Chemistry
Caroline M Gorvin, Angela Rogers, Michelle Stewart, Anju Paudyal, Tertius A Hough, Lydia Teboul, Sara Wells, Steve Dm Brown, Roger D Cox, Rajesh V Thakker
The adaptor protein-2 sigma subunit (AP2σ), encoded by AP2S1 , forms a heterotetrameric complex, with AP2α, AP2β, and AP2μ subunits, that is pivotal for clathrin-mediated endocytosis, and AP2σ loss-of-function mutations impair internalization of the calcium-sensing receptor (CaSR), a G-protein-coupled receptor, and cause familial hypocalciuric hypercalcemia type-3 (FHH3). Mice with AP2σ mutations that would facilitate investigations of the in vivo role of AP2σ, are not available, and we therefore embarked on establishing such mice...
May 2, 2017: JBMR Plus
Alzbeta Horvatova, Tanyarath Utaipan, Ann-Christin Otto, Yuling Zhang, Hongying Gan-Schreier, Petr Pavek, Anita Pathil, Wolfgang Stremmel, Walee Chamulitrat
The bile acid-phospholipid conjugate ursodeoxycholyl oleoyl-lysophophatidylethanolamide (UDCA-18:1LPE) is an anti-inflammatory and anti-fibrotic agent as previously shown in cultured hepatocytes and hepatic stellate cells as well as in in vivo models of liver injury. We hypothesize that UDCA-18:1LPE may directly inhibit the activation of immune cells. We found that UDCA-18:1LPE was capable of inhibiting the migration of phorbol ester-differentiated human THP-1 cells. We examined anti-inflammatory activity of UDCA-18:1LPE during activation of THP1-derived macrophages...
February 20, 2018: European Journal of Pharmacology
Kunpeng Liu, Lei Zhang, Qiang Zhao, Zhiyao Zhao, Feng Zhi, Yunfei Qin, Jun Cui
NF-κB signaling controls a large set of physiological processes ranging from inflammatory responses to cell death. Its activation is tightly regulated through controlling the activity and stability of multiple signaling components. Here, we identify that NF-κB activation is suppressed by an F-box protein, S-phase kinase associated protein 2 (SKP2). SKP2 deficiency enhanced NF-κB activation as well as the production of inflammatory cytokines. In addition, SKP2 potently blocked the NF-κB activation at the IκB kinase (IKK) level...
February 21, 2018: Journal of Molecular Cell Biology
María D Vázquez-Carretero, Pablo García-Miranda, María S Balda, Karl Matter, María J Peral, Anunciación A Ilundain
Disabled-1 (Dab1) is an essential intracellular adaptor protein in the reelin pathway. Our previous studies in mice intestine showed that Dab1 transmits the reelin signal to cytosolic signalling pathways. Here, we determine the Dab1 isoform expressed in rodent small and large intestine, its subcellular location and co-localization with clathrin, caveolin-1 and N-Wasp. PCR and sequencing analysis reveal that rodent small and large intestine express a Dab1 isoform that misses three (Y198 , Y200 and Y220 ) of the five tyrosine phosphorylation sites present in brain Dab1 isoform (canonical) and contains nuclear localization and export signals...
February 19, 2018: Biochimica et Biophysica Acta
Takao Sakaizawa, Tomio Matsumura, Chifumi Fujii, Shigeaki Hida, Masayuki Toishi, Takayuki Shiina, Kazuo Yoshida, Kazutoshi Hamanaka, Ken-Ichi Ito, Shun'ichiro Taniguchi
Primary lung cancer is the most frequent cause of cancer-related deaths worldwide. Cisplatin has been used as a key drug in the treatment for patients with lung cancer; however, most of the patients failed to respond to cisplatin within several months, and the mechanisms underlying the cisplatin resistance have not been fully elucidated. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is a key adaptor protein in the formation of inflammasomes. ASC is also involved in apoptotic signaling...
2018: Tohoku Journal of Experimental Medicine
Prashanta Kumar Panda, Prajna Paramita Naik, Prakash P Praharaj, Biswa Ranjan Meher, Piyush Kumar Gupta, Rama S Verma, Tapas K Maiti, Muthu K Shanmugam, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Gautam Sethi, Rajesh Agarwal, Sujit K Bhutia
Eradicating cancer stem cells (CSCs) in colorectal cancer (CRC) through differentiation therapy is a promising approach for cancer treatment. Our retrospective tumor-specimen analysis elucidated alteration in the expression of bone morphogenetic protein 2 (BMP-2) and β-catenin during the colon cancer progression, indicating that their possible intervention through "forced differentiation" in colon cancer remission. We reveal that Abrus agglutinin (AGG) induces the colon CSCs differentiation, enhancing sensitive to the anticancer therapeutics...
February 19, 2018: Molecular Carcinogenesis
Gil Katz, Kelsey Voss, Toria F Yan, Yong Chan Kim, Robert L Kortum, David W Scott, Andrew L Snow
Restimulation-induced cell death (RICD) is an apoptotic program that regulates effector T cell expansion, triggered by repeated stimulation through the T cell receptor (TCR) in the presence of interleukin-2 (IL-2). Although CD4+ regulatory T cells (Tregs) consume IL-2 and experience frequent TCR stimulation, they are highly resistant to RICD. Resistance in Tregs is dependent on the forkhead box P3 (FOXP3) transcription factor, although the mechanism remains unclear. T cells from patients with X-linked lymphoproliferative disease (XLP-1), that lack the adaptor molecule SLAM-associated protein (SAP), are also resistant to RICD...
February 12, 2018: Cellular Immunology
Geoffrey Guittard, Pierre Pontarotti, Samuel Granjeaud, Magda Rodrigues, Laurent Abi-Rached, Jacques A Nunès
Downstream of Kinase (DOK) proteins represent a multigenic family of adaptors that includes negative regulators of immune cell signaling. Using phylogenetics and intron/exon structure data, we show here that the seven human DOK genes (DOK1 to DOK7) form three highly divergent groups that emerged before the protostome-deuterostome split: DOK1/2/3, DOK4/5/6, and DOK7. For two of these three groups (DOK1/2/3 and DOK4/5/6), further gene duplications occurred in vertebrates and so while chordates only have three DOK genes, vertebrates have seven DOK genes over the three groups...
February 14, 2018: Developmental and Comparative Immunology
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