Activation of Adhesion GPCR EMR2/ADGRE2 Induces

Total Page:16

File Type:pdf, Size:1020Kb

Activation of Adhesion GPCR EMR2/ADGRE2 Induces ORIGINAL RESEARCH published: 03 April 2017 doi: 10.3389/fimmu.2017.00373 Activation of Adhesion GPCR EMR2/ ADGRE2 Induces Macrophage Differentiation and inflammatory Responses via Gα16/Akt/MAPK/ NF-κB Signaling Pathways Kuan-Yu I1, Yi-Shu Huang1†, Ching-Hsun Hu1, Wen-Yi Tseng2†, Chia-Hsin Cheng1, Martin Stacey3, Siamon Gordon1,4, Gin-Wen Chang1 and Hsi-Hsien Lin1,5,6* Edited by: 1 Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan, 2 Division of Céline Cougoule, Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital-Keelung, Keelung, Taiwan, 3 Faculty of Biological Centre national de la recherche Sciences, School of Molecular and Cellular Biology, University of Leeds, Leeds, UK, 4 Sir William Dunn School of Pathology, scientifique (CNRS), France University of Oxford, Oxford, UK, 5 Department of Anatomic Pathology, Chang Gung Memorial Hospital-Linkou, Taoyuan, Reviewed by: Taiwan, 6 Chang Gung Immunology Consortium, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan Frédéric Velard, Université de Reims Champagne- Ardenne, France EMR2/ADGRE2 is a human myeloid-restricted adhesion G protein-coupled receptor crit- Junjie Zhang, ically implicated in vibratory urticaria, a rare type of allergy caused by vibration-induced University of Southern California, USA mast cell activation. In addition, EMR2 is also highly expressed by monocyte/macro- *Correspondence: phages and has been linked to neutrophil migration and activation. Despite these findings, Hsi-Hsien Lin [email protected] little is known of EMR2-mediated signaling and its role in myeloid biology. In this report, †Present address: we show that activation of EMR2 via a receptor-specific monoclonal antibody promotes Yi-Shu Huang and Wen-Yi Tseng, the differentiation of human THP-1 monocytic cell line and induces the expression of Kennedy Institute of Rheumatology, pro-inflammatory mediators, including IL-8, TNF- , and MMP-9. Using specific signaling University of Oxford, Oxford, UK α inhibitors and siRNA knockdowns, biochemical and functional analyses reveal that the Specialty section: EMR2-mediated signaling is initiated by Gα16, followed by the subsequent activation of This article was submitted Akt, extracellular signal-regulated kinase, c-Jun N-terminal kinase, and nuclear factor to Inflammation, a section of the journal kappa-light-chain-enhancer of activated B cells. Our results demonstrate a functional Frontiers in Immunology role for EMR2 in the differentiation and inflammatory activation of human monocytic cells Received: 23 December 2016 and provide potential targets for myeloid cell-mediated inflammatory disorders. Accepted: 15 March 2017 Published: 03 April 2017 Keywords: cytokine, EMR2, GPCR, macrophage, inflammation, signaling Citation: I K-Y, Huang Y-S, Hu C-H, Abbreviations: aGPCR, adhesion GPCR; CM, conditioned medium; CTF, C-terminal fragment; DAG, diacylglycerol; DC, Tseng W-Y, Cheng C-H, Stacey M, dendritic cell; ECD, extracellular domain; EMR2, EGF-like module-containing mucin-like hormone receptor-like 2; ERK, Gordon S, Chang G-W and Lin H-H extracellular signal-regulated kinase; f-MLF, N-formyl-methionyl-leucyl-phenylalanine; GAIN, GPCR autoproteolysis-induc- (2017) Activation of Adhesion GPCR ing; GPCR, G protein-coupled receptor; GPS, GPCR proteolysis site; IP3, inositol triphosphate; JNK, c-Jun N-terminal kinase; EMR2/ADGRE2 Induces Macrophage LPA, lysophosphatidic acid; LPE, lysophosphatidylethanolamine; LPS, lipopolysaccharide; Mφ, macrophage; mAb, monoclo- Differentiation and Inflammatory nal antibody; MAPK, Mitogen-activated protein kinases; MMP, matrix metalloproteinases; Mo, monocyte; Nφ, neutrophil; Responses via Gα16 /Akt/MAPK/ NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; NTF, N-terminal fragment; PLC, phospholipase C; NF-κB Signaling Pathways. PMA, phorbol 12-myristate 13-acetate; PI3K, Phosphoinositide 3-kinase; PIP2, phosphatidylinositol biphosphate; PIP3, phos- Front. Immunol. 8:373. phatidylinositol 3,4,5 trisphosphate; PTX, pertussis toxin; ROS, reactive oxygen species; SIRS, systemic inflammatory response doi: 10.3389/fimmu.2017.00373 syndrome; TNF, tumor necrosis factor; 7TM, seven transmembrane. Frontiers in Immunology | www.frontiersin.org 1 April 2017 | Volume 8 | Article 373 I et al. EMR2 Signaling in Monocytic Cell INTRODUCTION protein motifs and a GPCR autoproteolysis-inducing (GAIN) domain (20–22). During receptor biosynthesis, aGPCRs are nor- Professional phagocytes such as macrophages (Mφ), neutrophils mally bisected at a consensus GPCR proteolysis site via the GAIN (Nφ), and dendritic cells (DCs) are critical for the recognition domain-mediated autoproteolytic reaction into a N-terminal and elimination of invading pathogens (1, 2). The processes of ECD-fragment (NTF) and a C-terminal 7TM-fragment (CTF), phagocytosis as well as the subsequent microbial killing and which remain conjugated as a dual-subunit receptor (13, immune activation/resolution by these innate immune effector 21). Recent advances indicate that aGPCR activation is likely cells are largely mediated via a diverse array of receptors and their mediated by ligand-induced NTF displacement, followed by signaling reactions (1, 3). In this regard, one receptor of interest the unfolding and binding of an internal agonist peptide to is EMR2/ADGRE2, a human myeloid-restricted adhesion G the 7TM core of CTF (23, 24). The mechanistic insights of the protein-coupled receptor (aGPCR) highly homologous to F4/80, “tethered agonism” of aGPCRs are increasingly being unraveled, the widely acclaimed surface marker that defines murine tissue including the coupling of unique G proteins to distinct aGPCR Mφ (4–6). members (21, 25–27). However, an orderly depiction of aGPCR- As a human ortholog of F4/80, EMR2 similarly contains mediated signaling pathways is currently lacking. In the present multiple epidermal growth factor-like modules in its extracellular report, we investigated and identified the involvement of αG 16/ domain (ECD), which binds to its endogenous ligand dermatan Akt/mitogen-activated protein kinase (MAPK)/nuclear factor sulfate (4, 7, 8). Initially identified as a myeloid-restricted tran- kappa-light-chain-enhancer of activated B cells (NF-κB) in script expressed in monocytes (Mos)/Mφ, Nφ, and myeloid DC EMR2 receptor-mediated signaling. Our results indicate that (4), EMR2 protein expression was later shown to be upregulated EMR2 activation/signaling plays a functional role in the dif- during the in vitro differentiation of φM but downregulated ferentiation and inflammatory activation of human monocytic following DC maturation (9). On the other hand, the strongest cells. The EMR2-induced signaling cascades reported here may in vivo EMR2 protein signal was detected in CD16+ blood Mos help identify potential targets for the therapeutic management and BDCA-3+ myeloid DC (10). Foamy Mφ in atherosclerotic of inflammatory disorders, such as SIRS and vibratory urticaria. vessels and splenic Gaucher cells are highly EMR2-positive, whereas multiple sclerosis brain foam cells express little if any EMR2 (11). The differential expression patterns of EMR2 in MATERIALS AND METHODS distinct myeloid populations strongly suggest a regulatory role of EMR2 in myeloid cell function (12, 13). Reagents and Antibodies Indeed, binding and activation of EMR2 by a ECD-specific All chemicals and reagents were purchased from Sigma-Aldrich 2A1 monoclonal antibody (mAb) strongly enhanced the inflam- (St. Louis, MO, USA) unless otherwise specified. Anti-mAbs matory responses of Nφ to a panel of stimuli, while 2A1 treatment used for Western blotting against extracellular signal-regulated alone (without inflammatory stimuli) did not seem effective kinase (ERK)1/2, p-ERK1/2, p38, p-p38 (Thr180/Tyr182), (14). In addition, 2A1-induced EMR2 activation was shown to c-Jun N-terminal kinase (JNK), p-JNK (Thr183/Tyr185), κI B-α, modulate the production of multiple cytokines and survival of p-IκB-α (Ser32), p-Ikkα/β (Ser176/180), and p-Akt (Ser473) were lipopolysaccharide-stimulated Nφ (15). Hence, EMR2 activation obtained from Cell Signaling Technology (Beverly, MA, USA). seems to have a priming effect on φN activation. Furthermore, Anti-Gα16 mAb was from Abcam (Cambridge, UK). Anti-F(ab′)2 upregulated EMR2 expression was identified in φN of patients fragment goat anti-mouse (GAM) IgG (H + L) was from Jackson suffering from systemic inflammatory response syndrome (SIRS), ImmunoResearch (West Grove, PA, USA). Anti-CD11b-PE, anti- and a significant association was noted between the percentage CD62L-PE, anti-CD81-PE, anti-CD9-APC, and anti-CD4-FITC of EMR2-expressing Nφ and the extent of organ failure in SIRS for flow cytometry and anti-phosphotyrosine, anti-β-actin mAb patients. As a result, EMR2 was proposed recently as a novel Nφ for Western blotting were purchased from BD Biosciences. The biomarker for SIRS (14, 16). A more recent study demonstrated mAbs used for cell stimulation were 2A1 (EMR2-specific mAb) that Nφ of liver cirrhosis patients with infection have higher (AbD Serotec) and mouse monoclonal IgG1 (Clone 11711) (R&D EMR2 expression levels, which showed strong correlation with System) as described previously (18). disease severity and predicted overall mortality (17). Likewise, we previously showed that Mφ activated by 2A1-induced Cell Culture EMR2 ligation promoted secretion of several pro-inflammatory THP-1 (ATCC®TIB-202™), HL-60 (ATCC®CCL-240™), and cytokines (18). More recently,
Recommended publications
  • Edinburgh Research Explorer
    Edinburgh Research Explorer International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein-coupled receptor list Citation for published version: Davenport, AP, Alexander, SPH, Sharman, JL, Pawson, AJ, Benson, HE, Monaghan, AE, Liew, WC, Mpamhanga, CP, Bonner, TI, Neubig, RR, Pin, JP, Spedding, M & Harmar, AJ 2013, 'International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein-coupled receptor list: recommendations for new pairings with cognate ligands', Pharmacological reviews, vol. 65, no. 3, pp. 967-86. https://doi.org/10.1124/pr.112.007179 Digital Object Identifier (DOI): 10.1124/pr.112.007179 Link: Link to publication record in Edinburgh Research Explorer Document Version: Publisher's PDF, also known as Version of record Published In: Pharmacological reviews Publisher Rights Statement: U.S. Government work not protected by U.S. copyright General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Download date: 02. Oct. 2021 1521-0081/65/3/967–986$25.00 http://dx.doi.org/10.1124/pr.112.007179 PHARMACOLOGICAL REVIEWS Pharmacol Rev 65:967–986, July 2013 U.S.
    [Show full text]
  • General Discussion
    UvA-DARE (Digital Academic Repository) EGF-TM7 receptors: A diverse and still evolving family of receptors on the leukocyte surface Matmati, M. Publication date 2008 Link to publication Citation for published version (APA): Matmati, M. (2008). EGF-TM7 receptors: A diverse and still evolving family of receptors on the leukocyte surface. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl) Download date:23 Sep 2021 Chapter 6 General Discussion GENERAL DISCUSSION Since their identification, starting about 15 years ago, a growing amount of data has accumulated about the structure, the expression, the ligands and, more recently, also the functional implications of EGF-TM7 receptors. Studies with antibody treatment and gene targeting in mice and antibody treatment of human cells in vitro, led to the implication of EGF-TM7 receptors in the trafficking of granulocytes, the generation of efferent antigen specific regulatory T cells and the potentiation of different granulocyte effector functions [1-4].
    [Show full text]
  • Flow Reagents Single Color Antibodies CD Chart
    CD CHART CD N° Alternative Name CD N° Alternative Name CD N° Alternative Name Beckman Coulter Clone Beckman Coulter Clone Beckman Coulter Clone T Cells B Cells Granulocytes NK Cells Macrophages/Monocytes Platelets Erythrocytes Stem Cells Dendritic Cells Endothelial Cells Epithelial Cells T Cells B Cells Granulocytes NK Cells Macrophages/Monocytes Platelets Erythrocytes Stem Cells Dendritic Cells Endothelial Cells Epithelial Cells T Cells B Cells Granulocytes NK Cells Macrophages/Monocytes Platelets Erythrocytes Stem Cells Dendritic Cells Endothelial Cells Epithelial Cells CD1a T6, R4, HTA1 Act p n n p n n S l CD99 MIC2 gene product, E2 p p p CD223 LAG-3 (Lymphocyte activation gene 3) Act n Act p n CD1b R1 Act p n n p n n S CD99R restricted CD99 p p CD224 GGT (γ-glutamyl transferase) p p p p p p CD1c R7, M241 Act S n n p n n S l CD100 SEMA4D (semaphorin 4D) p Low p p p n n CD225 Leu13, interferon induced transmembrane protein 1 (IFITM1). p p p p p CD1d R3 Act S n n Low n n S Intest CD101 V7, P126 Act n p n p n n p CD226 DNAM-1, PTA-1 Act n Act Act Act n p n CD1e R2 n n n n S CD102 ICAM-2 (intercellular adhesion molecule-2) p p n p Folli p CD227 MUC1, mucin 1, episialin, PUM, PEM, EMA, DF3, H23 Act p CD2 T11; Tp50; sheep red blood cell (SRBC) receptor; LFA-2 p S n p n n l CD103 HML-1 (human mucosal lymphocytes antigen 1), integrin aE chain S n n n n n n n l CD228 Melanotransferrin (MT), p97 p p CD3 T3, CD3 complex p n n n n n n n n n l CD104 integrin b4 chain; TSP-1180 n n n n n n n p p CD229 Ly9, T-lymphocyte surface antigen p p n p n
    [Show full text]
  • ADGRE2-NTF Is Regulated by Site- Specific N-Glycosylation
    www.nature.com/scientificreports OPEN Membrane-association of EMR2/ ADGRE2-NTF is regulated by site- specifc N-glycosylation Received: 19 December 2017 Yi-Shu Huang1,4, Nien-Yi Chiang1, Gin-Wen Chang1 & Hsi-Hsien Lin1,2,3 Accepted: 27 February 2018 The evolutionarily conserved adhesion G protein-coupled receptors (aGPCRs) play critical roles in Published: xx xx xxxx biological processes as diverse as brain development, cell polarity and innate immune functions. A defning feature of aGPCRs is the GPCR autoproteolysis inducing (GAIN) domain capable of self- catalytic cleavage, resulting in the generation of an extracellular N-terminal fragment (NTF) and a seven-transmembrane C-terminal fragment (CTF) involved in the cellular adhesion and signaling functions, respectively. Interestingly, two diferent NTF subtypes have previously been identifed, namely an NTF that couples non-covalently with the CTF and a membrane-associated NTF that tethers on cell surface independently. The two NTF subtypes are expected to regulate aGPCR signaling via distinct mechanisms however their molecular characteristics are largely unknown. Herein, the membrane-associated NTF of EMR2/ADGRE2 is investigated and found to be modifed by diferential N-glycosylation. The membrane association of EMR2-NTF occurs in post-ER compartments and site- specifc N-glycosylation in the GAIN domain is involved in modulating its membrane-association ability. Finally, a unique amphipathic α-helix in the GAIN domain is identifed as a putative membrane anchor of EMR2-NTF. These results provide novel insights into the complex interaction and activation mechanisms of aGPCRs. Characterized by a long extracellular domain (ECD) with cell-adhesion functions and a seven-transmembrane (7TM) domain with signaling functions, the adhesion G protein-coupled receptors (aGPCRs) have been impli- cated in diverse biological activities and human diseases1.
    [Show full text]
  • An Overview on G Protein-Coupled Receptor-Induced Signal Transduction in Acute Myeloid Leukemia
    An overview on G protein-coupled receptor-induced signal transduction in Acute Myeloid Leukemia 1* 1,3 4,5,6 2* Frode Selheim , Elise Aasebø , Catalina Ribas and Anna M. Aragay 1The Proteomics Unit at the University of Bergen, Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5020 Bergen, Norway; 3 Department of Clinical Science, University of Bergen, Jonas Lies vei 87, 5021 Bergen, Norway; [email protected]. 2Departamento de Biologia Celular. Instituto de Biología Molecular de Barcelona (IBMB-CSIC), Spanish National Research Council (CSIC), Baldiri i Reixac, 15, 08028 Barcelona, Spain; [email protected]. 4Departamento de Biología Molecular and Centro de Biología Molecular “Severo Ochoa” (UAM-CSIC), 28049 Madrid, Spain; 5Instituto de Investigación Sanitaria La Princesa, 28006 Madrid, Spain; 6CIBER de Enfermedades Cardiovasculares, ISCIII (CIBERCV), 28029 Madrid, Spain, [email protected] * Corresponding authors: Frode Selheim Adr: Jonas Lies vei 91, 5020 Bergen, Norway Email: [email protected], Tel:+4755586091 Anna M. Aragay Adr: Baldiri i Reixac, 15, 08028 Barcelona. Spain. E-mail: [email protected]; Tel.: +934098671 1 Abstract Background: Acute myeloid leukemia (AML) is a genetically heterogeneous disease characterized by uncontrolled proliferation of precursor myeloid-lineage cells in the bone marrow. AML is also characterized with patients with poor long-term survival outcomes due to relapse. Many efforts have been made to understand the biological heterogeneity of AML and the challenges to develop new therapies are therefore enormous. G protein-coupled receptors (GPCRs) are a large attractive drug targeted family of transmembrane proteins, and aberrant GPCR expression and GPCR-mediated signaling have been implicated in leukemogenesis of AML.
    [Show full text]
  • Biased Signaling of G Protein Coupled Receptors (Gpcrs): Molecular Determinants of GPCR/Transducer Selectivity and Therapeutic Potential
    Pharmacology & Therapeutics 200 (2019) 148–178 Contents lists available at ScienceDirect Pharmacology & Therapeutics journal homepage: www.elsevier.com/locate/pharmthera Biased signaling of G protein coupled receptors (GPCRs): Molecular determinants of GPCR/transducer selectivity and therapeutic potential Mohammad Seyedabadi a,b, Mohammad Hossein Ghahremani c, Paul R. Albert d,⁎ a Department of Pharmacology, School of Medicine, Bushehr University of Medical Sciences, Iran b Education Development Center, Bushehr University of Medical Sciences, Iran c Department of Toxicology–Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Iran d Ottawa Hospital Research Institute, Neuroscience, University of Ottawa, Canada article info abstract Available online 8 May 2019 G protein coupled receptors (GPCRs) convey signals across membranes via interaction with G proteins. Origi- nally, an individual GPCR was thought to signal through one G protein family, comprising cognate G proteins Keywords: that mediate canonical receptor signaling. However, several deviations from canonical signaling pathways for GPCR GPCRs have been described. It is now clear that GPCRs can engage with multiple G proteins and the line between Gprotein cognate and non-cognate signaling is increasingly blurred. Furthermore, GPCRs couple to non-G protein trans- β-arrestin ducers, including β-arrestins or other scaffold proteins, to initiate additional signaling cascades. Selectivity Biased Signaling Receptor/transducer selectivity is dictated by agonist-induced receptor conformations as well as by collateral fac- Therapeutic Potential tors. In particular, ligands stabilize distinct receptor conformations to preferentially activate certain pathways, designated ‘biased signaling’. In this regard, receptor sequence alignment and mutagenesis have helped to iden- tify key receptor domains for receptor/transducer specificity.
    [Show full text]
  • Multi-Functionality of Proteins Involved in GPCR and G Protein Signaling: Making Sense of Structure–Function Continuum with In
    Cellular and Molecular Life Sciences (2019) 76:4461–4492 https://doi.org/10.1007/s00018-019-03276-1 Cellular andMolecular Life Sciences REVIEW Multi‑functionality of proteins involved in GPCR and G protein signaling: making sense of structure–function continuum with intrinsic disorder‑based proteoforms Alexander V. Fonin1 · April L. Darling2 · Irina M. Kuznetsova1 · Konstantin K. Turoverov1,3 · Vladimir N. Uversky2,4 Received: 5 August 2019 / Revised: 5 August 2019 / Accepted: 12 August 2019 / Published online: 19 August 2019 © Springer Nature Switzerland AG 2019 Abstract GPCR–G protein signaling system recognizes a multitude of extracellular ligands and triggers a variety of intracellular signal- ing cascades in response. In humans, this system includes more than 800 various GPCRs and a large set of heterotrimeric G proteins. Complexity of this system goes far beyond a multitude of pair-wise ligand–GPCR and GPCR–G protein interactions. In fact, one GPCR can recognize more than one extracellular signal and interact with more than one G protein. Furthermore, one ligand can activate more than one GPCR, and multiple GPCRs can couple to the same G protein. This defnes an intricate multifunctionality of this important signaling system. Here, we show that the multifunctionality of GPCR–G protein system represents an illustrative example of the protein structure–function continuum, where structures of the involved proteins represent a complex mosaic of diferently folded regions (foldons, non-foldons, unfoldons, semi-foldons, and inducible foldons). The functionality of resulting highly dynamic conformational ensembles is fne-tuned by various post-translational modifcations and alternative splicing, and such ensembles can undergo dramatic changes at interaction with their specifc partners.
    [Show full text]
  • Development and Validation of a Protein-Based Risk Score for Cardiovascular Outcomes Among Patients with Stable Coronary Heart Disease
    Supplementary Online Content Ganz P, Heidecker B, Hveem K, et al. Development and validation of a protein-based risk score for cardiovascular outcomes among patients with stable coronary heart disease. JAMA. doi: 10.1001/jama.2016.5951 eTable 1. List of 1130 Proteins Measured by Somalogic’s Modified Aptamer-Based Proteomic Assay eTable 2. Coefficients for Weibull Recalibration Model Applied to 9-Protein Model eFigure 1. Median Protein Levels in Derivation and Validation Cohort eTable 3. Coefficients for the Recalibration Model Applied to Refit Framingham eFigure 2. Calibration Plots for the Refit Framingham Model eTable 4. List of 200 Proteins Associated With the Risk of MI, Stroke, Heart Failure, and Death eFigure 3. Hazard Ratios of Lasso Selected Proteins for Primary End Point of MI, Stroke, Heart Failure, and Death eFigure 4. 9-Protein Prognostic Model Hazard Ratios Adjusted for Framingham Variables eFigure 5. 9-Protein Risk Scores by Event Type This supplementary material has been provided by the authors to give readers additional information about their work. Downloaded From: https://jamanetwork.com/ on 10/02/2021 Supplemental Material Table of Contents 1 Study Design and Data Processing ......................................................................................................... 3 2 Table of 1130 Proteins Measured .......................................................................................................... 4 3 Variable Selection and Statistical Modeling ........................................................................................
    [Show full text]
  • Chapter 2 the EGF-TM7 Family
    UvA-DARE (Digital Academic Repository) CD97 and EMR2: receptors on the move Kwakkenbos, M.J. Publication date 2004 Link to publication Citation for published version (APA): Kwakkenbos, M. J. (2004). CD97 and EMR2: receptors on the move. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl) Download date:08 Oct 2021 Chapter 2 The EGF-TM7 family: a postgenomic view Immunogenetics, 55: 655-666, 2004 Mark J. Kwakkenbos1, Else N. Kop1,2, Martin Stacey3, Mourad Matmati1, Siamon Gordon3, Hsi-Hsien Lin3 and Jörg Hamann1 laboratory for Experimental Immunology 2Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands 3Sir William Dunn School of Pathology, University of Oxford, Oxford, U.K. Chapter 2 ABSTRACT With the human and mouse genome projects now completed, the receptor repertoire of mammalian cells has finally been elucidated.
    [Show full text]
  • Human CD Marker Chart Reviewed by HLDA1 Bdbiosciences.Com/Cdmarkers
    BD Biosciences Human CD Marker Chart Reviewed by HLDA1 bdbiosciences.com/cdmarkers 23-12399-01 CD Alternative Name Ligands & Associated Molecules T Cell B Cell Dendritic Cell NK Cell Stem Cell/Precursor Macrophage/Monocyte Granulocyte Platelet Erythrocyte Endothelial Cell Epithelial Cell CD Alternative Name Ligands & Associated Molecules T Cell B Cell Dendritic Cell NK Cell Stem Cell/Precursor Macrophage/Monocyte Granulocyte Platelet Erythrocyte Endothelial Cell Epithelial Cell CD Alternative Name Ligands & Associated Molecules T Cell B Cell Dendritic Cell NK Cell Stem Cell/Precursor Macrophage/Monocyte Granulocyte Platelet Erythrocyte Endothelial Cell Epithelial Cell CD1a R4, T6, Leu6, HTA1 b-2-Microglobulin, CD74 + + + – + – – – CD93 C1QR1,C1qRP, MXRA4, C1qR(P), Dj737e23.1, GR11 – – – – – + + – – + – CD220 Insulin receptor (INSR), IR Insulin, IGF-2 + + + + + + + + + Insulin-like growth factor 1 receptor (IGF1R), IGF-1R, type I IGF receptor (IGF-IR), CD1b R1, T6m Leu6 b-2-Microglobulin + + + – + – – – CD94 KLRD1, Kp43 HLA class I, NKG2-A, p39 + – + – – – – – – CD221 Insulin-like growth factor 1 (IGF-I), IGF-II, Insulin JTK13 + + + + + + + + + CD1c M241, R7, T6, Leu6, BDCA1 b-2-Microglobulin + + + – + – – – CD178, FASLG, APO-1, FAS, TNFRSF6, CD95L, APT1LG1, APT1, FAS1, FASTM, CD95 CD178 (Fas ligand) + + + + + – – IGF-II, TGF-b latency-associated peptide (LAP), Proliferin, Prorenin, Plasminogen, ALPS1A, TNFSF6, FASL Cation-independent mannose-6-phosphate receptor (M6P-R, CIM6PR, CIMPR, CI- CD1d R3G1, R3 b-2-Microglobulin, MHC II CD222 Leukemia
    [Show full text]
  • Robles JTO Supplemental Digital Content 1
    Supplementary Materials An Integrated Prognostic Classifier for Stage I Lung Adenocarcinoma based on mRNA, microRNA and DNA Methylation Biomarkers Ana I. Robles1, Eri Arai2, Ewy A. Mathé1, Hirokazu Okayama1, Aaron Schetter1, Derek Brown1, David Petersen3, Elise D. Bowman1, Rintaro Noro1, Judith A. Welsh1, Daniel C. Edelman3, Holly S. Stevenson3, Yonghong Wang3, Naoto Tsuchiya4, Takashi Kohno4, Vidar Skaug5, Steen Mollerup5, Aage Haugen5, Paul S. Meltzer3, Jun Yokota6, Yae Kanai2 and Curtis C. Harris1 Affiliations: 1Laboratory of Human Carcinogenesis, NCI-CCR, National Institutes of Health, Bethesda, MD 20892, USA. 2Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo 104-0045, Japan. 3Genetics Branch, NCI-CCR, National Institutes of Health, Bethesda, MD 20892, USA. 4Division of Genome Biology, National Cancer Center Research Institute, Tokyo 104-0045, Japan. 5Department of Chemical and Biological Working Environment, National Institute of Occupational Health, NO-0033 Oslo, Norway. 6Genomics and Epigenomics of Cancer Prediction Program, Institute of Predictive and Personalized Medicine of Cancer (IMPPC), 08916 Badalona (Barcelona), Spain. List of Supplementary Materials Supplementary Materials and Methods Fig. S1. Hierarchical clustering of based on CpG sites differentially-methylated in Stage I ADC compared to non-tumor adjacent tissues. Fig. S2. Confirmatory pyrosequencing analysis of DNA methylation at the HOXA9 locus in Stage I ADC from a subset of the NCI microarray cohort. 1 Fig. S3. Methylation Beta-values for HOXA9 probe cg26521404 in Stage I ADC samples from Japan. Fig. S4. Kaplan-Meier analysis of HOXA9 promoter methylation in a published cohort of Stage I lung ADC (J Clin Oncol 2013;31(32):4140-7). Fig. S5. Kaplan-Meier analysis of a combined prognostic biomarker in Stage I lung ADC.
    [Show full text]
  • (EGF-TM7) Receptor CD97 the Epidermal Growth Factor-Seven
    The Epidermal Growth Factor-Seven Transmembrane (EGF-TM7) Receptor CD97 Is Required for Neutrophil Migration and Host Defense This information is current as of September 23, 2021. Jaklien C. Leemans, Anje A. te Velde, Sandrine Florquin, Roelof J. Bennink, Kora de Bruin, René A. W. van Lier, Tom van der Poll and Jörg Hamann J Immunol 2004; 172:1125-1131; ; doi: 10.4049/jimmunol.172.2.1125 Downloaded from http://www.jimmunol.org/content/172/2/1125 References This article cites 52 articles, 19 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/172/2/1125.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 23, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2004 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology The Epidermal Growth Factor-Seven Transmembrane (EGF-TM7) Receptor CD97 Is Required for Neutrophil Migration and Host Defense1 Jaklien C.
    [Show full text]