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Adaptor protein 2

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https://www.readbyqxmd.com/read/28713858/life-stage-specific-cargo-receptors-facilitate-glycosylphosphatidylinositol-anchored-surface-coat-protein-transport-in-trypanosoma-brucei
#1
Emilia K Kruzel, George P Zimmett, James D Bangs
The critical virulence factor of bloodstream-form Trypanosoma brucei is the glycosylphosphatidylinositol (GPI)-anchored variant surface glycoprotein (VSG). Endoplasmic reticulum (ER) exit of VSG is GPI dependent and relies on a discrete subset of COPII machinery (TbSec23.2/TbSec24.1). In other systems, p24 transmembrane adaptor proteins selectively recruit GPI-anchored cargo into nascent COPII vesicles. Trypanosomes have eight putative p24s (TbERP1 to TbERP8) that are constitutively expressed at the mRNA level...
July 2017: MSphere
https://www.readbyqxmd.com/read/28712573/ve-cadherin-phosphorylation-regulates-endothelial-fluid-shear-stress-responses-through-the-polarity-protein-lgn
#2
Daniel E Conway, Brian G Coon, Madhusuthan Budatha, Paul T Arsenovic, Fabrizio Orsenigo, Florian Wessel, Jiasheng Zhang, Zhenwu Zhuang, Elisabetta Dejana, Dietmar Vestweber, Martin A Schwartz
Fluid shear stress due to blood flow on the vascular endothelium regulates blood vessel development, remodeling, physiology, and pathology [1, 2]. A complex consisting of PECAM-1, VE-cadherin, and vascular endothelial growth factor receptors (VEGFRs) that resides at endothelial cell-cell junctions transduces signals important for flow-dependent vasodilation, blood vessel remodeling, and atherosclerosis. PECAM-1 transduces forces to activate src family kinases (SFKs), which phosphorylate and transactivate VEGFRs [3-5]...
July 10, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28703133/association-of-autoimmune-hepatitis-with-src-homology-2-adaptor-protein-3-gene-polymorphisms-in-japanese-patients
#3
Takeji Umemura, Satoru Joshita, Hideaki Hamano, Kaname Yoshizawa, Shigeyuki Kawa, Eiji Tanaka, Masao Ota
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease characterized by an autoimmune reaction to hepatocytes. The Src homology 2 adaptor protein 3 (SH2B3) gene is a member of the SH2B family of adaptor proteins that has been implicated in the integration and regulation of multiple signaling events. SH2B3 is involved in cytokine signaling pathways and serves as a negative mediator of T-cell receptor signaling. Genome-wide association analyses in Caucasians have linked a missense mutation at rs3184504 in SH2B3 with AIH...
July 13, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28701864/induction-of-forkhead-class-box-o3a-and-apoptosis-by-a-standardized-ginsenoside-formulation-kg-135-is-potentiated-by-autophagy-blockade-in-a549-human-lung-cancer-cells
#4
Chih-Jung Yao, Jyh-Ming Chow, Shuang-En Chuang, Chia-Lun Chang, Ming-De Yan, Hsin-Lun Lee, I-Chun Lai, Pei-Chun Lin, Gi-Ming Lai
BACKGROUND: KG-135, a standardized formulation enriched with Rk1, Rg3, and Rg5 ginsenosides, has been shown to inhibit various types of cancer cells; however, the underlying mechanisms are not fully understood. In this study, we explored its effects in A549 human lung cancer cells to investigate the induction of Forkhead Class box O3a (FOXO3a) and autophagy. METHODS: Cell viability was determined by sulforhodamine B staining. Apoptosis and cell cycle distribution were analyzed using flow cytometry...
July 2017: Journal of Ginseng Research
https://www.readbyqxmd.com/read/28701375/spata2-regulates-the-activation-of-ripk1-by-modulating-linear-ubiquitination
#5
Ran Wei, Lily Wen Xu, Jianping Liu, Yanxia Li, Pei Zhang, Bing Shan, Xiaojuan Lu, Lihui Qian, Zheming Wu, Kangyun Dong, Hong Zhu, Lifeng Pan, Junying Yuan, Heling Pan
Stimulation of cells with TNFα leads to the formation of the TNF-R1 signaling complex (TNF-RSC) to mediate downstream cellular fate decision. Activation of the TNF-RSC is modulated by different types of ubiquitination and may lead to cell death, including apoptosis and necroptosis, in both RIPK1-dependent and RIPK1-independent manners. Spata2 (spermatogenesis-associated 2) is an adaptor protein recruited into the TNF-RSC to modulate the interaction between the linear ubiquitin chain assembly complex (LUBAC) and the deubiquitinase CYLD (cylindromatosis)...
July 12, 2017: Genes & Development
https://www.readbyqxmd.com/read/28699640/lfa-1-activates-focal-adhesion-kinases-fak1-pyk2-to-generate-lat-grb2-skap1-complexes-that-terminate-t-cell-conjugate-formation
#6
Monika Raab, Yuning Lu, Karsten Kohler, Xin Smith, Klaus Strebhardt, Christopher E Rudd
Lymphocyte function-associated antigen 1 (LFA-1) affinity and avidity changes have been assumed to mediate adhesion to intercellular adhesion molecule-1 for T-cell conjugation to dendritic cells (DC). Although the T-cell receptor (TCR) and LFA-1 can generate intracellular signals, the immune cell adaptor protein linker for the activation of T cells (LAT) couples the TCR to downstream events. Here, we show that LFA-1 can mediate both adhesion and de-adhesion, dependent on receptor clustering. Although increased affinity mediates adhesion, LFA-1 cross-linking induced the association and activation of the protein-tyrosine kinases FAK1/PYK1 that phosphorylated LAT selectively on a single Y-171 site for the binding to adaptor complex GRB-2-SKAP1...
July 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28691777/structure-and-evolution-of-enth-and-vhs-enth-like-domains-in-tepsin
#7
Tara L Archuleta, Meredith N Frazier, Anderson E Monken, Amy K Kendall, Joel Harp, Airlie J McCoy, Nicole Creanza, Lauren P Jackson
Tepsin is currently the only accessory trafficking protein identified in adaptor-related protein 4 (AP4) coated vesicles originating at the trans-Golgi network (TGN). The molecular basis for interactions between AP4 subunits and motifs in the tepsin C-terminus have been characterized, but the biological role of tepsin remains unknown. We determined X-ray crystal structures of the tepsin ENTH and VHS/ENTH-like domains. Our data reveal unexpected structural features that suggest key functional differences between these and similar domains in other trafficking proteins...
July 10, 2017: Traffic
https://www.readbyqxmd.com/read/28687632/increased-levels-of-gab1-and-gab2-adaptor-proteins-skew-il-4-signaling-toward-m2-macrophage-driven-pulmonary-fibrosis-in-mice
#8
Xiaohong Guo, Tingting Li, Yun Xu, Xiayan Xu, Zhengyi Zhu, Yun Zhang, Jiaqi Xu, Kaihong Xu, Hongqiang Cheng, Xue Zhang, Yuehai Ke
M2-polarized macrophages, also known as alternatively activated macrophages, have long been associated with pulmonary fibrosis; however, the mechanism has not been fully defined. Gab1 and Gab2 proteins belong to the GAB family of adaptors and are integral components of the signal specificity in response to various extracellular stimuli. In this report, we found that levels of both Gab1 and Gab2 were elevated in M2-polarized macrophages isolated from bleomycin-induced fibrotic lungs. In vitro Gab1/2 deficiency in bone marrow-derived macrophages abrogated IL-4-mediated M2 polarization...
July 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28687362/the-unexpected-function-of-a-highly-conserved-yxx%C3%AE-motif-in-hcv-core-protein
#9
Eirini Karamichali, Elisavet Serti, Aikaterini Gianneli, Aikaterini Papaefthymiou, Athanassios Kakkanas, Pelagia Foka, Alexandros Seremetakis, Konstantina Katsarou, Ioannis P Trougakos, Urania Georgopoulou
Hepatitis C virus (HCV) is an RNA positive strand virus, member of the Flaviviridae family. The HCV viral particle is composed of a capsid containing the genome, surrounded by an endoplasmic reticulum (ER)-derived lipid bilayer where E1 and E2 are assembled as heterodimers. However, different forms of viral particles have been identified in the serum of HCV-infected patients, including non-enveloped particles. Previous reports have demonstrated that HCV non-enveloped capsid-like particles (HCVne) can be generated by HCV core protein sequence...
July 4, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28686357/homozygous-null-variant-in-cradd-encoding-an-adaptor-protein-that-mediates-apoptosis-is-associated-with-lissencephaly
#10
Tamar Harel, Nuphar Hacohen, Avraham Shaag, Moshe Gomori, Amihood Singer, Orly Elpeleg, Vardiella Meiner
Lissencephaly is a severe malformation of cortical development, most often attributed to abnormalities in neuronal migration. It is associated with a severe prognosis including developmental delay, intellectual disability, and seizures. Lissencephaly can be reliably diagnosed during late gestation by neurosonography or fetal magnetic resonance imaging (MRI). We report two sibling male fetuses who were diagnosed with delayed cortical sulcation highly suggestive of lissencephaly during late pregnancy. After receiving genetic counseling, the parents elected to terminate the pregnancies based on the neuroradiological findings and the associated severe prognosis...
July 7, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28678595/the-unc-53-gene-negatively-regulates-rac-gtpases-to-inhibit-unc-5-activity-during-distal-tip-cell-migrations-in-c-elegans
#11
Amita Pandey, Vipul Yadav, Aditi Sharma, Jitendra P Khurana, Girdhar K Pandey
The unc-53/NAV2 gene encodes for an adaptor protein required for cell migrations along the anteroposterior (AP) axes of C. elegans. This study identifies unc-53 as a novel component of signaling pathways regulating distal tip cell (DTC) migrations along the AP and dorsoventral (DV) axes. unc-53 negatively regulates and functions downstream of ced-10/Rac pathway genes; ced-10/Rac and mig-2/RhoG, which are required for proper DTC migration. Moreover, unc-53 exhibits genetic interaction with abl-1 and unc-5, the two known negative regulators of ced-10/Rac signaling...
July 5, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28663580/an-atlas-of-bloodstream-accessible-bone-marrow-proteins-for-site-directed-therapy-of-acute-myeloid-leukemia
#12
L Angenendt, S Reuter, D Kentrup, A S Benk, F Neumann, J Hüve, A C Martens, C Schwöppe, T Kessler, L H Schmidt, T Sauer, C Brand, J-H Mikesch, G Lenz, R M Mesters, C Müller-Tidow, W Hartmann, E Wardelmann, D Neri, W E Berdel, C Roesli, C Schliemann
The concept of arming antibodies with bioactive payloads for a site-specific therapy of cancer has gained considerable interest in recent years. However, a successful antibody-based targeting approach critically relies on the availability of a tumor-associated target, which is not only preferentially expressed in the tumor tissue but which is also easily accessible for antibody therapeutics coming from the bloodstream. Here, we perfused the vasculature of healthy and acute myeloid leukemia (AML)-bearing rats with a reactive ester derivative of biotin and subsequently quantified the biotinylated proteins to identify AML-associated bone marrow (BM) antigens accessible from the bloodstream...
June 30, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28663238/remarkable-evolutionary-conservation-of-anti-obesity-adipose-wdtc1-homologs-in-animals-and-plants
#13
Eric Ducos, Valentin Vergès, Thomas Dugé de Bernonville, Nathalie Blanc, Nathalie Giglioli-Guivarc'h, Christelle Dutilleul
ASG2 (Altered Seed Germination 2) is a prenylated protein in Arabidopsis thaliana that participates to abscisic acid signaling and is proposed to act as a substrate adaptor for the DDB1-CUL4 E3 ubiquitin ligase complex. ASG2 harbors WD40 and TetratricoPeptide Repeat (TPR) domains, and resembles the well-conserved animal gene called ADP (anti-obesity factor ADIPOSE) in fly and WDTC1 (WD40 and TPR 1) in humans. Loss of function of WDTC1 results in an increase in adipocytes, fat accumulation and obesity. Anti-adipogenic functions of WDTC1 involve regulation of fat-related gene transcription, notably through its binding to histone deacetylases...
June 29, 2017: Genetics
https://www.readbyqxmd.com/read/28662348/abnormal-wnt5a-signaling-causes-mandibular-hypoplasia-in-robinow-syndrome
#14
S Hosseini-Farahabadi, S J Gignac, A Danescu, K Fu, J M Richman
The study of rare genetic diseases provides valuable insights into human gene function. Here, we investigate dominant Robinow syndrome (RS), which affects the WNT5A signaling pathway. Autosomal dominant RS is caused by missense mutations in WNT5A or nonsense mutations in the adaptor protein DVL1 or DVL3. The recessive form of the disease is caused by loss-of-function mutations in the receptor ROR2. RS is characterized by hypertelorism, midface, and mandibular hypoplasia. Here, we focus on the missense mutations in WNT5A, since the impact on function is difficult to predict from in silico analysis...
June 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28659552/differential-effects-of-myocardial-afadin-on-pressure-overload-induced-compensated-cardiac-hypertrophy
#15
Dimitar P Zankov, Akira Sato, Akio Shimizu, Hisakazu Ogita
BACKGROUND: Pressure overload induces cardiac hypertrophy, which often ends in heart failure. Afadin is an adaptor protein that is ubiquitously expressed and, in the heart, it localizes at intercalated disks. The current study aimed to examine the afadin-mediated cardiac phenotype in mice exposed to different types of pressure overload: transverse aortic constriction (TAC) burden and angiotensin II (Ang II) stimulation.Methods and Results:Conditional knockout mice with selective deletion of afadin (afadin cKO) in cardiomyocytes were generated...
June 28, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28656966/e3-ubiquitin-ligase-znrf4-negatively-regulates-nod2-signalling-and-induces-tolerance-to-mdp
#16
Pradeep Bist, Wan Shoo Cheong, Aylwin Ng, Neha Dikshit, Bae-Hoon Kim, Niyas Kudukkil Pulloor, Hanif Javanmard Khameneh, Matija Hedl, Avinash R Shenoy, Vanniarajan Balamuralidhar, Najib Bin Abdul Malik, Michelle Hong, Albert Neutzner, Keh-Chuang Chin, Koichi S Kobayashi, Antonio Bertoletti, Alessandra Mortellaro, Clara Abraham, John D MacMicking, Ramnik J Xavier, Bindu Sukumaran
Optimal regulation of the innate immune receptor nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is essential for controlling bacterial infections and inflammatory disorders. Chronic NOD2 stimulation induces non-responsiveness to restimulation, termed NOD2-induced tolerance. Although the levels of the NOD2 adaptor, RIP2, are reported to regulate both acute and chronic NOD2 signalling, how RIP2 levels are modulated is unclear. Here we show that ZNRF4 induces K48-linked ubiquitination of RIP2 and promotes RIP2 degradation...
June 28, 2017: Nature Communications
https://www.readbyqxmd.com/read/28652408/the-extreme-c-terminal-region-of-kindlin-2-is-critical-to-its-regulation-of-integrin-activation
#17
Jamila Hirbawi, Katarzyna Bialkowska, Kamila M Bledzka, Jianmin Liu, Koichi Fukuda, Jun Qin, Edward F Plow
Kindlin-2 (K2), a 4.1R-ezrin-radixin-moesin (FERM) domain adaptor protein, mediates numerous cellular responses, including integrin activation. The C-terminal 15 amino acid sequence of K2 is remarkably conserved across species but is absent in canonical FERM proteins including talin. In CHO cells expressing integrin αIIbβ3, co-expression of K2 with talin head (talin-H) domain resulted in robust integrin activation, but this co-activation was lost after deletion of as few as seven amino acids from the K2 C-terminus...
June 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28650106/dok3-modulates-bone-remodeling-by-negatively-regulating-osteoclastogenesis-and-positively-regulating-osteoblastogenesis
#18
Xiaofeng Cai, Junjie Xing, Courtney L Long, Qisheng Peng, Mary Beth Humphrey
Osteoclastogenesis is essential for bone remodeling and normal skeletal maintenance. RANKL promotes osteoclast differentiation and function but requires costimulation of immunoreceptor tyrosine-based activation motif (ITAM)-coupled immunoreceptors. Triggering receptor expressed on myeloid cells-2 (TREM2) coupled to ITAM-adaptor protein DNAX activation protein 12kDA (DAP12) provides costimulation of intracellular calcium signaling during osteoclastogenesis. Previously, we found that downstream of kinase-3 (DOK3) physically associates with DAP12 to inhibit toll-like receptor (TLR)-induced inflammatory signaling in macrophages...
June 26, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28639322/tnf-%C3%AE-induced-nod2-and-rip2-contribute-to-the-up-regulation-of-cytokines-induced-by-mdp-in-monocytic-thp-1-cells
#19
Xiaobin Chen, Zhilin Xiao, Xiumei Xie, Xueting Liu, Manli Jiang, Chuang Yuan, Li Yang, Jinyue Hu
Nucleotide-binding oligomerization domain containing 2 (NOD2)-induced signal transduction and cytokine production is regulated by a number of factors. However, the feedback effect of the pro-inflammatory TNF-α on NOD2-induced inflammation is not fully understood. In this study, we found unexpectedly that TNF-α up-regulated NOD2 ligand MDP-induced production of the CXC chemokines, including CXCL1, 2 and 8, and the pro-inflammatory cytokines, including IL-1β, IL-6 and TNF-α, in a dose-dependent manner at both mRNA and protein levels in monocytic THP-1 cells...
June 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28638935/jip1-and-jip3-cooperate-to-mediate-trkb-anterograde-axonal-transport-by-activating-kinesin-1
#20
Tao Sun, Yuan Li, Ting Li, Huixian Ma, Yunyun Guo, Xingyu Jiang, Ming Hou, Shuhong Huang, Zheyu Chen
Long-range anterograde axonal transport of TrkB is important for neurons to exert appropriate BDNF responses. TrkB anterograde axonal delivery is mediated by kinesin-1, which associates with TrkB via the adaptor protein JIP3 or the Slp1/Rab27B/CRMP-2 protein complex. However, little is known about the activation mechanisms of TrkB-loaded kinesin-1. Here, we show that JIP1 mediates TrkB anterograde axonal transport using JIP1 knockout mice, sciatic nerve ligation analysis and live imaging. Next, we proved that JIP1 and JIP3 cooperate to mediate TrkB anterograde axonal transport...
June 21, 2017: Cellular and Molecular Life Sciences: CMLS
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