SheddomeDB: the ectodomain shedding database for membrane-bound shed markers

BackgroundA number of membrane-anchored proteins are known to be released from cell surface via ectodomain shedding. The cleavage and release of membrane proteins has been shown to modulate various cellular processes and disease pathologies. Numerous studies revealed that cell membrane molecules of diverse functional groups are subjected to proteolytic cleavage, and the released soluble form of proteins may modulate various signaling processes. Therefore, in addition to the secreted protein markers that undergo secretion through the secretory pathway, the shed membrane proteins may comprise an additional resource of noninvasive and accessible biomarkers. In this context, identifying the membrane-bound proteins that will be shed has become important in the discovery of clinically noninvasive biomarkers. Nevertheless, a data repository for biological and clinical researchers to review the shedding information, which is experimentally validated, for membrane-bound protein shed markers is still lacking.ResultsIn this study, the database SheddomeDB was developed to integrate publicly available data of the shed membrane proteins. A comprehensive literature survey was performed to collect the membrane proteins that were verified to be cleaved or released in the supernatant by immunological-based validation experiments. From 436 studies on shedding, 401 validated shed membrane proteins were included, among which 199 shed membrane proteins have not been annotated or validated yet by existing cleavage databases. SheddomeDB attempted to provide a comprehensive shedding report, including the regulation of shedding machinery and the related function or diseases involved in the shedding events. In addition, our published tool ShedP was embedded into SheddomeDB to support researchers for predicting the shedding event on unknown or unrecorded membrane proteins.ConclusionsTo the best of our knowledge, SheddomeDB is the first database for the identification of experimentally validated shed membrane proteins and currently may provide the most number of membrane proteins for reviewing the shedding information. The database included membrane-bound shed markers associated with numerous cellular processes and diseases, and some of these markers are potential novel markers because they are not annotated or validated yet in other databases. SheddomeDB may provide a useful resource for discovering membrane-bound shed markers. The interactive web of SheddomeDB is publicly available at http://bal.ym.edu.tw/SheddomeDB/.

[1]  C. Blobel,et al.  Ectodomain shedding of the EGF‐receptor ligand epigen is mediated by ADAM17 , 2007, FEBS letters.

[2]  J. Arribas,et al.  Metastasis-associated C4.4A, a GPI-anchored protein cleaved by ADAM10 and ADAM17 , 2008, Biological chemistry.

[3]  T. Grosser,et al.  Deciphering the human platelet sheddome. , 2011, Blood.

[4]  S. M. Park,et al.  Proteolytic cleavage of extracellular secreted {alpha}-synuclein via matrix metalloproteinases. , 2005, The Journal of biological chemistry.

[5]  Oliver Schilling,et al.  Proteome-derived, database-searchable peptide libraries for identifying protease cleavage sites , 2008, Nature Biotechnology.

[6]  C. Blobel,et al.  Neuronal Brain-derived Neurotrophic Factor Is Synthesized in Excess, with Levels Regulated by Sortilin-mediated Trafficking and Lysosomal Degradation , 2011, The Journal of Biological Chemistry.

[7]  L. Rassenti,et al.  Free circulating soluble CD52 as a tumor marker in chronic lymphocytic leukemia and its implication in therapy with anti‐CD52 antibodies , 2004, Cancer.

[8]  H. Kitayama,et al.  RECK Forms Cowbell-shaped Dimers and Inhibits Matrix Metalloproteinase-catalyzed Cleavage of Fibronectin* , 2009, Journal of Biological Chemistry.

[9]  Corinna Cortes,et al.  Support-Vector Networks , 1995, Machine Learning.

[10]  R. Black,et al.  Photic injury promotes cleavage of p75NTR by TACE and nuclear trafficking of the p75 intracellular domain , 2007, Molecular and Cellular Neuroscience.

[11]  J. Scheller,et al.  T‐cell immunoglobulin and mucin domain 2 (TIM‐2) is a target of ADAM10‐mediated ectodomain shedding , 2014, The FEBS journal.

[12]  J. Tavernier,et al.  RNF41 (Nrdp1) controls type 1 cytokine receptor degradation and ectodomain shedding , 2011, Journal of Cell Science.

[13]  P. Jansen-Dürr,et al.  Two Functionally Distinct Isoforms of TL1A (TNFSF15) Generated by Differential Ectodomain Shedding , 2010, The journals of gerontology. Series A, Biological sciences and medical sciences.

[14]  L. Karlsson,et al.  Catalytic Activity of ADAM8, ADAM15, and MDC-L (ADAM28) on Synthetic Peptide Substrates and in Ectodomain Cleavage of CD23* , 2003, Journal of Biological Chemistry.

[15]  M. Atkinson,et al.  Nardilysin-Dependent Proteolysis of Cell-Associated VTCN1 (B7-H4) Marks Type 1 Diabetes Development , 2014, Diabetes.

[16]  J. C. Jamieson,et al.  Studies on the effect of lysosomotropic agents on the release of Gal beta 1-4GlcNAc alpha-2,6-sialytransferase from rat liver slices during the acute-phase response. , 1989, The Biochemical journal.

[17]  Samy Lamouille,et al.  TACE-mediated ectodomain shedding of the type I TGF-beta receptor downregulates TGF-beta signaling. , 2009, Molecular cell.

[18]  T. Pihlajaniemi,et al.  The shed ectodomain of type XIII collagen affects cell behaviour in a matrix-dependent manner. , 2004, The Biochemical journal.

[19]  A. Boyd,et al.  ADAM12-cleaved ephrin-A1 contributes to lung metastasis , 2014, Oncogene.

[20]  M. Stack,et al.  Membrane protease proteomics: Isotope-coded affinity tag MS identification of undescribed MT1-matrix metalloproteinase substrates. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[21]  M. Wills-Karp,et al.  Matrix metalloproteinase 8 contributes to solubilization of IL-13 receptor alpha2 in vivo. , 2008, The Journal of allergy and clinical immunology.

[22]  John P. Johnson,et al.  Epithelial Sodium Channels Are Activated by Furin-dependent Proteolysis* , 2004, Journal of Biological Chemistry.

[23]  C. Blobel,et al.  Metalloproteases regulate T‐cell proliferation and effector function via LAG‐3 , 2007, The EMBO journal.

[24]  G. Weskamp,et al.  Distinct roles for ADAM10 and ADAM17 in ectodomain shedding of six EGFR ligands , 2004, The Journal of cell biology.

[25]  S. Weggen,et al.  Formation of Pmel17 Amyloid Is Regulated by Juxtamembrane Metalloproteinase Cleavage, and the Resulting C-terminal Fragment Is a Substrate for γ-Secretase* , 2009, Journal of Biological Chemistry.

[26]  Thien Nguyen,et al.  Cleavage of myelin associated glycoprotein by matrix metalloproteinases , 2008, Journal of Neuroimmunology.

[27]  D. Spaner,et al.  Soluble CD200 is critical to engraft chronic lymphocytic leukemia cells in immunocompromised mice. , 2012, Cancer research.

[28]  James C. Powell,et al.  The insulin-like growth factor 1 (IGF-1) receptor is a substrate for gamma-secretase-mediated intramembrane proteolysis. , 2007, Biochemical and biophysical research communications.

[29]  Ruedi Aebersold,et al.  Systematic Proteomic Analysis Identifies β-Site Amyloid Precursor Protein Cleaving Enzyme 2 and 1 (BACE2 and BACE1) Substrates in Pancreatic β-Cells* , 2013, The Journal of Biological Chemistry.

[30]  T. Isobe,et al.  Membrane Type 1 Matrix Metalloproteinase (MT1-MMP/MMP-14) Cleaves and Releases a 22-kDa Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) Fragment from Tumor Cells* , 2006, Journal of Biological Chemistry.

[31]  Y. Azuma,et al.  Altered expression of glycoproteins on the cell surface of Jurkat cells during etoposide-induced apoptosis: shedding and intracellular translocation of glycoproteins. , 2009, Biochimica et biophysica acta.

[32]  A. Koch,et al.  Mediator of Angiogenesis Junctional Adhesion Molecule-C Is a Soluble , 2010 .

[33]  Eunkyung Kim,et al.  Soluble HLA-G generated by proteolytic shedding inhibits NK-mediated cell lysis. , 2004, Biochemical and biophysical research communications.

[34]  D. Wagner,et al.  Regulated surface expression and shedding support a dual role for semaphorin 4D in platelet responses to vascular injury , 2007, Proceedings of the National Academy of Sciences.

[35]  Y. Kanda,et al.  Binding of Delta1, Jagged1, and Jagged2 to Notch2 Rapidly Induces Cleavage, Nuclear Translocation, and Hyperphosphorylation of Notch2 , 2000, Molecular and Cellular Biology.

[36]  K. Chou.  Prediction of protein cellular attributes using pseudo‐amino acid composition , 2001, Proteins.

[37]  M. Lohse,et al.  Agonist-regulated Cleavage of the Extracellular Domain of Parathyroid Hormone Receptor Type 1* , 2010, The Journal of Biological Chemistry.

[38]  W. Falk,et al.  Soluble neuropilin-2, a nerve repellent receptor, is increased in rheumatoid arthritis synovium and aggravates sympathetic fiber repulsion and arthritis. , 2009, Arthritis and rheumatism.

[39]  N. Taniguchi,et al.  Identification of target proteins of N‐acetylglucosaminyl transferase V in human colon cancer and implications of protein tyrosine phosphatase kappa in enhanced cancer cell migration , 2006, Proteomics.

[40]  J. Fransen,et al.  Proteolytic processing of the receptor‐type protein tyrosine phosphatase PTPBR7 , 2007, The FEBS journal.

[41]  P. Galle,et al.  Cleavage of CD95 by matrix metalloproteinase-7 induces apoptosis resistance in tumour cells , 2004, Oncogene.

[42]  Y. Ma,et al.  Matrix metalloproteinase 2 releases active soluble ectodomain of fibroblast growth factor receptor 1. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[43]  F. Dorner,et al.  'Shed' furin: mapping of the cleavage determinants and identification of its C-terminus. , 2001, The Biochemical journal.

[44]  P. Saftig,et al.  Klotho is a substrate for α‐, β‐ and γ‐secretase , 2009 .

[45]  C. Enns,et al.  Matriptase-2- and Proprotein Convertase-cleaved Forms of Hemojuvelin Have Different Roles in the Down-regulation of Hepcidin Expression* , 2010, The Journal of Biological Chemistry.

[46]  I. Stamenkovic,et al.  CD44 anchors the assembly of matrilysin/MMP-7 with heparin-binding epidermal growth factor precursor and ErbB4 and regulates female reproductive organ remodeling. , 2002, Genes & development.

[47]  K. von Figura,et al.  Mannose 6-phosphate/insulin-like growth factor II-binding proteins in human serum and urine. Their relation to the mannose 6-phosphate/insulin-like growth factor II receptor. , 1988, The Biochemical journal.

[48]  M. Kuo,et al.  Expression and immunoaffinity purification of recombinant soluble human GPR56 protein for the analysis of GPR56 receptor shedding by ELISA. , 2015, Protein expression and purification.

[49]  G. Müller-Newen,et al.  Proteolytic Cleavage Governs Interleukin-11 Trans-signaling. , 2016, Cell reports.

[50]  A. Strongin,et al.  The Hemopexin-like C-terminal Domain of Membrane Type 1 Matrix Metalloproteinase Regulates Proteolysis of a Multifunctional Protein, gC1qR* , 2002, The Journal of Biological Chemistry.

[51]  F. Fahrenholz,et al.  Alcadein Cleavages by Amyloid β-Precursor Protein (APP) α- and γ-Secretases Generate Small Peptides, p3-Alcs, Indicating Alzheimer Disease-related γ-Secretase Dysfunction* , 2009, The Journal of Biological Chemistry.

[52]  H. Lemke,et al.  CD30 Shedding from Karpas 299 Lymphoma Cells Is Mediated by TNF-α-Converting Enzyme1 , 2000, The Journal of Immunology.

[53]  J. Lubkowski,et al.  The Structure of the Extracellular Domain of Triggering Receptor Expressed on Myeloid Cells Like Transcript-1 and Evidence for a Naturally Occurring Soluble Fragment* , 2006, Journal of Biological Chemistry.

[54]  C. Hinkle,et al.  Multiple metalloproteinases process protransforming growth factor-alpha (proTGF-alpha). , 2003, Biochemistry.

[55]  W. J. Esselman,et al.  Release of thy-1.2 and thy-1.1 from lymphoblastoid cells: partial characterization and antigenicity of shed material. , 1978, Journal of immunology.

[56]  K. Shirai,et al.  Enhanced circulating soluble LR11 in patients with diabetic retinopathy. , 2012, American journal of ophthalmology.

[57]  W. Stetler-Stevenson,et al.  CD97, an adhesion receptor on inflammatory cells, stimulates angiogenesis through binding integrin counterreceptors on endothelial cells. , 2005, Blood.

[58]  E. Futai,et al.  Tumor suppressor cell adhesion molecule 1 (CADM1) is cleaved by a disintegrin and metalloprotease 10 (ADAM10) and subsequently cleaved by γ-secretase complex. , 2012, Biochemical and biophysical research communications.

[59]  J. Gliemann,et al.  Tumour necrosis factor alpha-converting enzyme mediates ectodomain shedding of Vps10p-domain receptor family members. , 2006, The Biochemical journal.

[60]  M. Essler,et al.  Proteolytically Processed Soluble Tumor Endothelial Marker (TEM) 5 Mediates Endothelial Cell Survival during Angiogenesis by Linking Integrin αvβ3 to Glycosaminoglycans* , 2006, Journal of Biological Chemistry.

[61]  E. Gerner,et al.  Heat shock-induced shedding of cell surface integrins in A549 human lung tumor cells in culture. , 1994, Experimental cell research.

[62]  J. Krolewski,et al.  Regulated proteolysis of the IFNaR2 subunit of the interferon-alpha receptor , 2004, Oncogene.

[63]  K. Shirai,et al.  Enhanced circulating soluble LR11 in patients with coronary organic stenosis. , 2010, Atherosclerosis.

[64]  Claus-Werner Franzke,et al.  Shedding of Collagen XXIII Is Mediated by Furin and Depends on the Plasma Membrane Microenvironment* , 2007, Journal of Biological Chemistry.

[65]  I. Kanazawa,et al.  CLAC: a novel Alzheimer amyloid plaque component derived from a transmembrane precursor, CLAC‐P/collagen type XXV , 2002, The EMBO journal.

[66]  K. Matsumoto,et al.  Multiple sites of proteolytic cleavage to release soluble forms of hepatocyte growth factor activator inhibitor type 1 from a transmembrane form. , 1999, Journal of biochemistry.

[67]  L. Lum,et al.  Evidence for a Role of a Tumor Necrosis Factor-α (TNF-α)-converting Enzyme-like Protease in Shedding of TRANCE, a TNF Family Member Involved in Osteoclastogenesis and Dendritic Cell Survival* , 1999, Journal of Biological Chemistry.

[68]  W. Jia,et al.  Increased levels of soluble CD226 in sera accompanied by decreased membrane CD226 expression on peripheral blood mononuclear cells from cancer patients , 2009, BMC Immunology.

[69]  P. Kassner,et al.  Functional and structural analysis of VLA-4 integrin alpha 4 subunit cleavage. , 1992, The Journal of biological chemistry.

[70]  S. Kuruppu,et al.  Production of soluble Neprilysin by endothelial cells. , 2014, Biochemical and biophysical research communications.

[71]  L. Puskás,et al.  Cleavage of the human thyrotropin receptor by ADAM10 is regulated by thyrotropin , 2007, Journal of molecular recognition : JMR.

[72]  D. Hallahan,et al.  TNF-alpha and IL-1 upregulate membrane-bound and soluble E-selectin through a common pathway. , 1997, The Journal of surgical research.

[73]  J. Arribas,et al.  Protein ectodomain shedding. , 2002, Chemical reviews.

[74]  M. Zeegers,et al.  Protein shedding in urothelial bladder cancer: prognostic implications of soluble urinary EGFR and EpCAM , 2015, British Journal of Cancer.

[75]  Marion C Lanteri,et al.  Soluble T Cell Immunoglobulin Mucin Domain 3 Is Shed from CD8+ T Cells by the Sheddase ADAM10, Is Increased in Plasma during Untreated HIV Infection, and Correlates with HIV Disease Progression , 2015, Journal of Virology.

[76]  J. Tang,et al.  Maturation of secreted meprin alpha during biosynthesis: role of the furin site and identification of the COOH-terminal amino acids of the mouse kidney metalloprotease subunit. , 1998, Archives of biochemistry and biophysics.

[77]  P. Saftig,et al.  Regulated Proteolysis of NOTCH2 and NOTCH3 Receptors by ADAM10 and Presenilins , 2014, Molecular and Cellular Biology.

[78]  L. Romani,et al.  Soluble Collectin-12 (CL-12) Is a Pattern Recognition Molecule Initiating Complement Activation via the Alternative Pathway , 2015, The Journal of Immunology.

[79]  M. Fenech,et al.  Effect of tissue inhibitor of metalloproteinases 3 on DLK1 shedding in cultured human pre-adipocytes and implications for adipose tissue remodelling , 2015, The Lancet.

[80]  W. Schmiegel,et al.  A Soluble Form of the Giant Cadherin Fat1 Is Released from Pancreatic Cancer Cells by ADAM10 Mediated Ectodomain Shedding , 2014, PloS one.

[81]  A. Strongin,et al.  Insights into Ectodomain Shedding and Processing of Protein-tyrosine Pseudokinase 7 (PTK7)* , 2012, The Journal of Biological Chemistry.

[82]  K. Yokote,et al.  Tetraspanin CD9 modulates ADAM17-mediated shedding of LR11 in leukocytes , 2014, Experimental & Molecular Medicine.

[83]  J. Strominger,et al.  Shedding as a mechanism of down-modulation of CD14 on stimulated human monocytes. , 1991, Journal of immunology.

[84]  B. Turk,et al.  Identification of Cleavage Sites Leading to the Shed Form of the Anti-Aging Protein Klotho , 2014, Biochemistry.

[85]  M. Berndt,et al.  Controlled shedding of platelet glycoprotein (GP)VI and GPIb–IX–V by ADAM family metalloproteinases , 2007, Journal of thrombosis and haemostasis : JTH.

[86]  R. V. van Lier,et al.  The CD27 membrane receptor, a lymphocyte‐specific member of the nerve growth factor receptor family, gives rise to a soluble form by protein processing that does not involve receptor endocytosis , 1992, European journal of immunology.

[87]  S. Maekawa,et al.  Characterization of a Novel Rat Brain Glycosylphosphatidylinositol-anchored Protein (Kilon), a Member of the IgLON Cell Adhesion Molecule Family* , 1999, The Journal of Biological Chemistry.

[88]  M. Lappas,et al.  MMP-14 is expressed in preeclamptic placentas and mediates release of soluble endoglin. , 2012, The American journal of pathology.

[89]  V. Berezin,et al.  Neural cell adhesion molecule function is regulated by metalloproteinase‐mediated ectodomain release , 2005, Journal of neuroscience research.

[90]  G. Andrews,et al.  Novel Proteolytic Processing of the Ectodomain of the Zinc Transporter ZIP4 (SLC39A4) during Zinc Deficiency Is Inhibited by Acrodermatitis Enteropathica Mutations , 2008, Molecular and Cellular Biology.

[91]  J. Kere,et al.  Ectodysplasin is released by proteolytic shedding and binds to the EDAR protein. , 2001, Human molecular genetics.

[92]  J. Barbuto,et al.  Local secretion/shedding of tumor-derived CD83 molecules as a novel tumor escape mechanism. , 2008, Molecular immunology.

[93]  N. Hilschmann,et al.  Determination of the molecular structure of the human free secretory component. , 1991, Biological chemistry Hoppe-Seyler.

[94]  L. Hazrati,et al.  LIV-1 ZIP ectodomain shedding in prion-infected mice resembles cellular response to transition metal starvation. , 2012, Journal of molecular biology.

[95]  H. Salih,et al.  Release of MICB molecules by tumor cells: mechanism and soluble MICB in sera of cancer patients. , 2006, Human immunology.

[96]  A. Santoni,et al.  NKG2D and DNAM-1 Ligands: Molecular Targets for NK Cell-Mediated Immunotherapeutic Intervention in Multiple Myeloma , 2015, BioMed research international.

[97]  N. LaRusso,et al.  Proteolytic Cleavage and Nuclear Translocation of Fibrocystin Is Regulated by Intracellular Ca2+ and Activation of Protein Kinase C* , 2006, Journal of Biological Chemistry.

[98]  S. Canevari,et al.  The ALCAM Shedding by the Metalloprotease ADAM17/TACE Is Involved in Motility of Ovarian Carcinoma Cells , 2007, Molecular Cancer Research.

[99]  Derek C. Radisky,et al.  Mesotrypsin promotes malignant growth of breast cancer cells through shedding of CD109 , 2010, Breast Cancer Research and Treatment.

[100]  J. Alberola-Ila,et al.  Existence of a soluble form of CD50 (intercellular adhesion molecule-3) produced upon human lymphocyte activation. Present in normal human serum and levels are increased in the serum of systemic lupus erythematosus patients. , 1995, Journal of immunology.

[101]  B. Carey,et al.  Presenilin/γ-secretase and α-secretase-like peptidases cleave human MHC Class I proteins , 2007 .

[102]  J. Zieske,et al.  MMP9 cleavage of the β4 integrin ectodomain leads to recurrent epithelial erosions in mice , 2011, Journal of Cell Science.

[103]  R. Sluyter,et al.  Human P2X7 receptor activation induces the rapid shedding of CXCL16. , 2013, Biochemical and biophysical research communications.

[104]  Jung-Ah Lyu,et al.  Cleavage of the Wnt receptor Ryk regulates neuronal differentiation during cortical neurogenesis. , 2008, Developmental cell.

[105]  S. V. van Deventer,et al.  Abrogation of IFN‐γ mediated epithelial barrier disruption by serine protease inhibition , 2005 .

[106]  A. Slomiany,et al.  Helicobacter pylori-induced gastric mucosal TGF-α ectodomain shedding and EGFR transactivation involves Rac1/p38 MAPK-dependent TACE activation , 2015, Inflammopharmacology.

[107]  A. Ullrich,et al.  EGFR signaling leads to downregulation of PTP-LAR via TACE-mediated proteolytic processing. , 2006, Cellular signalling.

[108]  F. Pépin,et al.  ADAM10 Releases a Soluble Form of the GPNMB/Osteoactivin Extracellular Domain with Angiogenic Properties , 2010, PloS one.

[109]  Z. Ahmed,et al.  TACE‐induced cleavage of NgR and p75NTR in dorsal root ganglion cultures disinhibits outgrowth and promotes branching of neurites in the presence of inhibitory CNS myelin , 2006, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[110]  Rong Zeng,et al.  Sys-BodyFluid: a systematical database for human body fluid proteome research , 2008, Nucleic Acids Res..

[111]  Jan Krützfeldt,et al.  Tmem27: a cleaved and shed plasma membrane protein that stimulates pancreatic beta cell proliferation. , 2005, Cell metabolism.

[112]  B. Koo,et al.  The ADAM15 ectodomain is shed from secretory exosomes , 2015, BMB reports.

[113]  C. Hinkle,et al.  Multiple Metalloproteinases Process Protransforming Growth Factor-α (ProTGF-α)† , 2003 .

[114]  F. Hirota,et al.  Soluble Insulin Receptor Ectodomain Is Elevated in the Plasma of Patients With Diabetes , 2007, Diabetes.

[115]  E. Raines,et al.  Emerging roles for ectodomain shedding in the regulation of inflammatory responses , 2006, Journal of leukocyte biology.

[116]  Hiroshi Mamitsuka,et al.  Predictions of Cleavability of Calpain Proteolysis by Quantitative Structure-Activity Relationship Analysis Using Newly Determined Cleavage Sites and Catalytic Efficiencies of an Oligopeptide Array* , 2016, Molecular & Cellular Proteomics.

[117]  M. Bennett,et al.  2B4 (CD244) and CS1: novel members of the CD2 subset of the immunoglobulin superfamily molecules expressed on natural killer cells and other leukocytes , 2001, Immunological reviews.

[118]  N. Nalivaeva,et al.  Membrane targeting, shedding and protein interactions of brain acetylcholinesterase , 2011, Journal of neurochemistry.

[119]  C. Ruan,et al.  Shear-induced interaction of platelets with von Willebrand factor results in glycoprotein Ibalpha shedding. , 2009, American journal of physiology. Heart and circulatory physiology.

[120]  A. Bensussan,et al.  A Soluble Form of the MHC Class I-Specific CD160 Receptor Is Released from Human Activated NK Lymphocytes and Inhibits Cell-Mediated Cytotoxicity1 , 2007, The Journal of Immunology.

[121]  R. Wynn,et al.  Identification of ADAM10 as a major source of HER2 ectodomain sheddase activity in HER2 overexpressing breast cancer cells , 2006, Cancer biology & therapy.

[122]  Brian Chung,et al.  Linking Receptor-mediated Endocytosis and Cell Signaling , 2004, Journal of Biological Chemistry.

[123]  C. Becker-Pauly,et al.  Meprin α and meprin β: Procollagen proteinases in health and disease. , 2015, Matrix biology : journal of the International Society for Matrix Biology.

[124]  G. Germino,et al.  Characterization of cis-Autoproteolysis of Polycystin-1, the Product of Human Polycystic Kidney Disease 1 Gene* , 2007, Journal of Biological Chemistry.

[125]  R. Nagle,et al.  Integrin alpha6 cleavage: a novel modification to modulate cell migration. , 2007, Experimental cell research.

[126]  Amir Feizi,et al.  HCSD: the human cancer secretome database , 2015, Database J. Biol. Databases Curation.

[127]  S. Velleman,et al.  Effect of glypican-1 covalently attached chains on turkey myogenic satellite cell proliferation, differentiation, and fibroblast growth factor 2 responsiveness. , 2010, Poultry science.

[128]  D. Riddell,et al.  Characterization of the Ectodomain Shedding of the β-Site Amyloid Precursor Protein-cleaving Enzyme 1 (BACE1)* , 2003, Journal of Biological Chemistry.

[129]  Konstantinos J. Mavrakis,et al.  The Eph-Receptor A7 Is a Soluble Tumor Suppressor for Follicular Lymphoma , 2011, Cell.

[130]  Yong Zhang,et al.  SPD—a web-based secreted protein database , 2004, Nucleic Acids Res..

[131]  J G Flanagan,et al.  Regulated cleavage of a contact-mediated axon repellent. , 2000, Science.

[132]  H. Ploegh,et al.  Comparison of amino acid sequences of two human histocompatibility antigens, HLA-A2 and HLA-B7: location of putative alloantigenic sites. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[133]  Z. Ye,et al.  Soluble member(s) of the mesothelin/megakaryocyte potentiating factor family are detectable in sera from patients with ovarian carcinoma. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[134]  P. Lamy,et al.  HER2 shedding and serum HER2 extracellular domain: biology and clinical utility in breast cancer. , 2012, Cancer treatment reviews.

[135]  J. Strominger,et al.  Metalloprotease and serine protease are involved in cleavage of CD43, CD44, and CD16 from stimulated human granulocytes. Induction of cleavage of L-selectin via CD16. , 1994, Journal of immunology.

[136]  T. Yoshizaki,et al.  Cleavage of Syndecan-1 by Membrane Type Matrix Metalloproteinase-1 Stimulates Cell Migration* , 2003, Journal of Biological Chemistry.

[137]  A. Gruber,et al.  Impaired autoproteolytic cleavage of mCLCA6, a murine integral membrane protein expressed in enterocytes, leads to cleavage at the plasma membrane instead of the endoplasmic reticulum , 2012, Molecules and cells.

[138]  S. B. Kim,et al.  Soluble epithin/PRSS14 secreted from cancer cells contains active angiogenic potential , 2010, Molecules and cells.

[139]  S. Ayuso‐Dolado,et al.  Brain ischaemia induces shedding of a BDNF‐scavenger ectodomain from TrkB receptors by excitotoxicity activation of metalloproteinases and γ‐secretases , 2016, The Journal of pathology.

[140]  Lian Shen,et al.  Ectodomain shedding of Fcα receptor is mediated by ADAM10 and ADAM17 , 2010, Immunology.

[141]  P. Saftig,et al.  Activity-dependent α-Cleavage of Nectin-1 Is Mediated by A Disintegrin and Metalloprotease 10 (ADAM10)* , 2010, The Journal of Biological Chemistry.

[142]  M. Beal,et al.  DJ-1 cleavage by matrix metalloproteinase 3 mediates oxidative stress-induced dopaminergic cell death. , 2011, Antioxidants & redox signaling.

[143]  M. Okada,et al.  Increased ectodomain shedding of cell adhesion molecule 1 as a cause of type II alveolar epithelial cell apoptosis in patients with idiopathic interstitial pneumonia , 2015, Respiratory Research.

[144]  M. Glocker,et al.  B cell activation leads to shedding of complement receptor type II (CR2/CD21) , 2003, European journal of immunology.

[145]  C. Blobel,et al.  Adam Meets Eph: An ADAM Substrate Recognition Module Acts as a Molecular Switch for Ephrin Cleavage In trans , 2005, Cell.

[146]  U. Petäjä-Repo,et al.  The Parkinson's-disease-associated receptor GPR37 undergoes metalloproteinase-mediated N-terminal cleavage and ectodomain shedding , 2016, Journal of Cell Science.

[147]  R. Hillenbrand,et al.  Zinc metalloproteinase-mediated cleavage of the human Nogo-66 receptor , 2004, Journal of Cell Science.

[148]  L. Muller,et al.  Soluble Form of the (Pro)Renin Receptor Generated by Intracellular Cleavage by Furin Is Secreted in Plasma , 2009, Hypertension.

[149]  G. Gorodeski.  Estrogen decrease in tight junctional resistance involves matrix-metalloproteinase-7-mediated remodeling of occludin. , 2007, Endocrinology.

[150]  F. Levi-Schaffer,et al.  CD48: A co-stimulatory receptor of immunity. , 2011, The international journal of biochemistry & cell biology.

[151]  T. O'Connor,et al.  Transmembrane semaphorin5B is proteolytically processed into a repulsive neural guidance cue , 2012, Journal of neurochemistry.

[152]  J. Peschon,et al.  Tumor necrosis factor-alpha-converting enzyme controls surface expression of c-Kit and survival of embryonic stem cell-derived mast cells. , 2004, The Journal of biological chemistry.

[153]  Y. Nakanishi,et al.  Endogenous metalloprotease solubilizes IL-13 receptor alpha2 in airway epithelial cells. , 2007, Biochemical and biophysical research communications.

[154]  H. Neumann,et al.  Sequential Proteolytic Processing of the Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) Protein by Ectodomain Shedding and γ-Secretase-dependent Intramembranous Cleavage* , 2013, The Journal of Biological Chemistry.

[155]  C. Haass,et al.  Trafficking and proteolytic processing of APP. , 2012, Cold Spring Harbor perspectives in medicine.

[156]  K. Berer,et al.  This information is current as Activation in Autoimmunity Released by ADAM 10 and Reflects B Cell The Immunoregulator Soluble TACI Is Lichtenthaler and , 2014 .

[157]  M. A. Sutton,et al.  Synapse Maturation by Activity-Dependent Ectodomain Shedding of SIRPα , 2013, Nature Neuroscience.

[158]  M. Tessier-Lavigne,et al.  Function of an axonal chemoattractant modulated by metalloprotease activity. , 2000, Science.

[159]  S. Rafii,et al.  VEGF-A Stimulates ADAM17-Dependent Shedding of VEGFR2 and Crosstalk Between VEGFR2 and ERK Signaling , 2008, Circulation research.

[160]  C. Blobel,et al.  Tumor necrosis factor-alpha-converting enzyme (ADAM17) mediates the cleavage and shedding of fractalkine (CX3CL1). , 2001, The Journal of biological chemistry.

[161]  S. Ku,et al.  Rosmarinic acid down-regulates endothelial protein C receptor shedding in vitro and in vivo. , 2013, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[162]  P. Kiener,et al.  Soluble CD137 (4-1BB) Ligand Is Released Following Leukocyte Activation and Is Found in Sera of Patients with Hematological Malignancies1 , 2001, The Journal of Immunology.

[163]  P. Fuerst,et al.  A Novel Mouse Dscam Mutation Inhibits Localization and Shedding of DSCAM , 2012, PloS one.

[164]  K. Matsumura,et al.  Characterization of the protease activity that cleaves the extracellular domain of beta-dystroglycan. , 2006, Biochemical and biophysical research communications.

[165]  Lin Ying Liu,et al.  Decreased Expression of Membrane IL-5 Receptor α on Human Eosinophils: II. IL-5 Down-Modulates Its Receptor Via a Proteinase-Mediated Process1 , 2002, The Journal of Immunology.

[166]  K. Sayama,et al.  Ectodomain Shedding of Lymphatic Vessel Endothelial Hyaluronan Receptor 1 (LYVE-1) Is Induced by Vascular Endothelial Growth Factor A (VEGF-A)* , 2016, The Journal of Biological Chemistry.

[167]  N. Villamor,et al.  Identification of a natural soluble form of human CD5. , 1999, Tissue antigens.

[168]  N. Alfaidy,et al.  Protocadherin-12 Cleavage Is a Regulated Process Mediated by ADAM10 Protein , 2011, The Journal of Biological Chemistry.

[169]  A. Ben-Ze'ev,et al.  The shed ectodomain of Nr-CAM stimulates cell proliferation and motility, and confers cell transformation. , 2005, Cancer research.

[170]  Olivier Barré,et al.  Proteomic Analyses Reveal an Acidic Prime Side Specificity for the Astacin Metalloprotease Family Reflected by Physiological Substrates , 2011, Molecular & Cellular Proteomics.

[171]  S. Luo,et al.  Increased Soluble CD4 in Serum of Rheumatoid Arthritis Patients Is Generated by Matrix Metalloproteinase (MMP)-Like Proteinases , 2013, PloS one.

[172]  B. Leuenberger,et al.  Phorbol 12-Myristate 13-Acetate-induced Ectodomain Shedding and Phosphorylation of the Human Meprinβ Metalloprotease* , 2003, Journal of Biological Chemistry.

[173]  M. Bernardo,et al.  Differential Inhibition of Membrane Type 3 (MT3)-Matrix Metalloproteinase (MMP) and MT1-MMP by Tissue Inhibitor of Metalloproteinase (TIMP)-2 and TIMP-3 Regulates Pro-MMP-2 Activation* , 2004, Journal of Biological Chemistry.

[174]  R. Andrews,et al.  Platelet receptor expression and shedding: glycoprotein Ib-IX-V and glycoprotein VI. , 2014, Transfusion medicine reviews.

[175]  F. Fahrenholz,et al.  Shedding of the amyloid precursor protein‐like protein APLP2 by disintegrin‐metalloproteinases , 2005, The FEBS journal.

[176]  L. Tomasello,et al.  Identification of Protein Tyrosine Phosphatase Receptor Gamma Extracellular Domain (sPTPRG) as a Natural Soluble Protein in Plasma , 2015, PloS one.

[177]  A. Thathiah,et al.  MT1-MMP mediates MUC1 shedding independent of TACE/ADAM17. , 2004, The Biochemical journal.

[178]  S. Shapiro,et al.  Matrix metalloproteinases cleave tissue factor pathway inhibitor. Effects on coagulation. , 2000, The Journal of biological chemistry.

[179]  E. Lo,et al.  The N-terminal ectodomain of Ninjurin1 liberated by MMP9 has chemotactic activity. , 2012, Biochemical and biophysical research communications.

[180]  J. Nalbantoglu,et al.  The Coxsackievirus and Adenovirus Receptor (CAR) Undergoes Ectodomain Shedding and Regulated Intramembrane Proteolysis (RIP) , 2013, PloS one.

[181]  E. Kojro,et al.  Receptor for Advanced Glycation End Products Is Subjected to Protein Ectodomain Shedding by Metalloproteinases* , 2008, Journal of Biological Chemistry.

[182]  Y. Komada,et al.  Shedding of CD9 antigen in acute lymphoblastic leukemia. , 1994, Leukemia and Lymphoma.

[183]  A. Iwase,et al.  ADAMs, a disintegrin and metalloproteinases, mediate shedding of oxytocinase. , 2004, Biochemical and biophysical research communications.

[184]  C. Géraud,et al.  Posttranslational proteolytic processing of Leda-1/Pianp involves cleavage by MMPs, ADAM10/17 and gamma-secretase. , 2016, Biochemical and biophysical research communications.

[185]  P. Levitt,et al.  The limbic system-associated membrane protein is an Ig superfamily member that mediates selective neuronal growth and axon targeting , 1995, Neuron.

[186]  M. Röllinghoff,et al.  A soluble form of the murine common gamma chain is present at high concentrations in vivo and suppresses cytokine signaling. , 2001, Blood.

[187]  B. Schermer,et al.  Extracellular Phosphorylation of Collagen XVII by Ecto-Casein Kinase 2 Inhibits Ectodomain Shedding* , 2007, Journal of Biological Chemistry.

[188]  Daniel C. Lee,et al.  Cardiomyocytes induce macrophage receptor shedding to suppress phagocytosis. , 2015, Journal of molecular and cellular cardiology.

[189]  N. Seidah,et al.  Increased proteolytic processing of protein tyrosine phosphatase mu in confluent vascular endothelial cells: the role of PC5, a member of the subtilisin family. , 1996, Biochemistry.

[190]  Xi Chen,et al.  Novel mechanistic insights into ectodomain shedding of EGFR Ligands Amphiregulin and TGF-α: impact on gastrointestinal cancers driven by secondary bile acids. , 2014, Cancer research.

[191]  A. Sehara-Fujisawa,et al.  Roles of ADAM8 in elimination of injured muscle fibers prior to skeletal muscle regeneration , 2015, Mechanisms of Development.

[192]  R. Sakai,et al.  The C-terminus of ephrin-B1 regulates metalloproteinase secretion and invasion of cancer cells , 2007, Journal of Cell Science.

[193]  Yi Tang,et al.  Tumor-stroma interaction: positive feedback regulation of extracellular matrix metalloproteinase inducer (EMMPRIN) expression and matrix metalloproteinase-dependent generation of soluble EMMPRIN. , 2004, Molecular cancer research : MCR.

[194]  M. Stoffel,et al.  Kin of IRRE-like Protein 2 Is a Phosphorylated Glycoprotein That Regulates Basal Insulin Secretion* , 2015, The Journal of Biological Chemistry.

[195]  S. Ménard,et al.  Shedding of the 67‐kD laminin receptor by human cancer cells , 1996, Journal of cellular biochemistry.

[196]  N. Hooper,et al.  Nitric oxide inhibits the shedding of the glycosylphosphatidylinositol-anchored dipeptidase from porcine renal proximal tubules. , 2002, The Biochemical journal.

[197]  A. Vlahou,et al.  Secretome proteomics for discovery of cancer biomarkers. , 2010, Journal of proteomics.

[198]  S. Becker-Herman,et al.  CD74 is a member of the regulated intramembrane proteolysis-processed protein family. , 2005, Molecular biology of the cell.

[199]  M. Hollenberg,et al.  Proteinase-activated receptor-2 and human lung epithelial cells: disarming by neutrophil serine proteinases. , 2003, American journal of respiratory cell and molecular biology.

[200]  S. Carlsson,et al.  Characterization of a hydrophilic form of Thy-1 purified from human cerebrospinal fluid. , 1988, Journal of Biological Chemistry.

[201]  A. Sloan,et al.  Proteolytic cleavage of protein tyrosine phosphatase mu regulates glioblastoma cell migration. , 2009, Cancer research.

[202]  A. Tholey,et al.  2 ADP-Ribosyltransferase − of T Cell Ecto Proteolysis Controls the Substrate Specificity Nucleotide-Induced Membrane-Proximal , 2015 .

[203]  E. Dı́az-Rodrı́guez,et al.  Extracellular signal-regulated kinase phosphorylates tumor necrosis factor alpha-converting enzyme at threonine 735: a potential role in regulated shedding. , 2002, Molecular biology of the cell.

[204]  D. Hartmann,et al.  Associates with Gas6 in Mouse Serum Adam10-dependent Cleavage and Soluble Axl Is Generated by Supplemental Material , 2005 .

[205]  J. Eckel,et al.  Shedding of dipeptidyl peptidase 4 is mediated by metalloproteases and up‐regulated by hypoxia in human adipocytes and smooth muscle cells , 2014, FEBS letters.

[206]  Hiroshi Sato,et al.  Shedding of kidney injury molecule-1 by membrane-type 1 matrix metalloproteinase. , 2012, Journal of biochemistry.

[207]  D. Carey,et al.  Matrix metalloproteinase‐dependent shedding of syndecan‐3, a transmembrane heparan sulfate proteoglycan, in Schwann cells , 2003, Journal of neuroscience research.

[208]  P. Saftig,et al.  The "a disintegrin and metalloprotease" (ADAM) family of sheddases: physiological and cellular functions. , 2009, Seminars in cell & developmental biology.

[209]  J. Fujimoto,et al.  Immunochemical analysis of the released Leu-2 (T8) molecule , 1984, The Journal of experimental medicine.

[210]  U. Rescher,et al.  Proteolytic cleavage of annexin 1 by human leukocyte elastase. , 2006, Biochimica et biophysica acta.

[211]  W. Brackenbury,et al.  Voltage-gated Na+ channels: Potential for β subunits as therapeutic targets , 2008, Expert opinion on therapeutic targets.

[212]  H. Atkins,et al.  Identification and characterization of a soluble c-kit receptor produced by human hematopoietic cell lines. , 1995, Blood.

[213]  R. Fridman,et al.  Processing, shedding, and endocytosis of membrane type 1‐matrix metalloproteinase (MT1‐MMP) , 2004, Journal of cellular physiology.

[214]  M. Castagnola,et al.  Enzymatic processing of β‐dystroglycan recombinant ectodomain by MMP‐9: Identification of the main cleavage site , 2009, IUBMB life.

[215]  R. Koski,et al.  The Transforming Receptor Tyrosine Kinase, Axl, Is Post-translationally Regulated by Proteolytic Cleavage (*) , 1995, The Journal of Biological Chemistry.

[216]  V. V. van Hinsbergh,et al.  Proteolysis of the urokinase-type plasminogen activator receptor by metalloproteinase-12: implication for angiogenesis in fibrin matrices. , 2001, Blood.

[217]  Y. Komada,et al.  Shedding of CD9 antigen by bone marrow cells from patients with acute lymphoblastic leukaemia , 1992, British journal of haematology.

[218]  G. Blobe,et al.  Ectodomain shedding of TβRIII is required for TβRIII-mediated suppression of TGF-β signaling and breast cancer migration and invasion , 2014, Molecular biology of the cell.

[219]  David C. Lee,et al.  An essential role for ectodomain shedding in mammalian development. , 1998, Science.

[220]  H. Kantarjian,et al.  Circulating CD33 and its clinical value in acute leukemia. , 2010, Experimental hematology.

[221]  A. Ullrich,et al.  Cellular Redistribution of Protein Tyrosine Phosphatases LAR and PTPσ by Inducible Proteolytic Processing , 1997, The Journal of cell biology.

[222]  H. Tilg,et al.  Elevated circulating levels of soluble interleukin-1 receptor type II during interleukin-2 immunotherapy. , 1999, European cytokine network.

[223]  B. de Strooper,et al.  ADAM10 cleavage of N‐cadherin and regulation of cell–cell adhesion and β‐catenin nuclear signalling , 2005, The EMBO journal.

[224]  R. V. van Lier,et al.  Shear Stress–Dependent Downregulation of the Adhesion-G Protein–Coupled Receptor CD97 on Circulating Leukocytes upon Contact with Its Ligand CD55 , 2013, The Journal of Immunology.

[225]  Hiroshi Asanuma,et al.  Cardiac hypertrophy is inhibited by antagonism of ADAM12 processing of HB-EGF: Metalloproteinase inhibitors as a new therapy , 2002, Nature Medicine.

[226]  G. Butler,et al.  The Soluble Catalytic Domain of Membrane Type 1 Matrix Metalloproteinase Cleaves the Propeptide of Progelatinase A and Initiates Autoproteolytic Activation , 1996, The Journal of Biological Chemistry.

[227]  S. Inui,et al.  Paracrine regulation of growth factor signaling by shed leucine-rich repeats and immunoglobulin-like domains 1. , 2011, Experimental cell research.

[228]  G. Johnson,et al.  Regulated proteolytic processing of LRP6 results in release of its intracellular domain , 2007, Journal of neurochemistry.

[229]  Bin Zhang,et al.  NK cell CD16 surface expression and function is regulated by a disintegrin and metalloprotease-17 (ADAM17). , 2013, Blood.

[230]  D. Schreiner,et al.  Processing of the human protocadherin Fat1 and translocation of its cytoplasmic domain to the nucleus. , 2005, Experimental cell research.

[231]  V. Hearing,et al.  The secreted form of a melanocyte membrane‐bound glycoprotein (Pmel17/gp100) is released by ectodomain shedding , 2010, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[232]  B. Zetter,et al.  Type XXIII Collagen, a New Transmembrane Collagen Identified in Metastatic Tumor Cells* , 2003, Journal of Biological Chemistry.

[233]  S. Yamamoto,et al.  Structure and expression of human thrombomodulin, a thrombin receptor on endothelium acting as a cofactor for protein C activation. , 1987, The EMBO journal.

[234]  H. Lemke,et al.  CD30 shedding from Karpas 299 lymphoma cells is mediated by TNF-alpha-converting enzyme. , 2000, Journal of immunology.

[235]  F. Jursky,et al.  Calpain‐mediated proteolytic cleavage of the neuronal glycine transporter, GlyT2 , 2003, Journal of neurochemistry.

[236]  K. Nakanishi,et al.  Ectodomain shedding of neuroglycan C, a brain‐specific chondroitin sulfate proteoglycan, by TIMP‐2‐ and TIMP‐3‐sensitive proteolysis , 2007, Journal of neurochemistry.

[237]  J. Hanna,et al.  Biological function of the soluble CEACAM1 protein and implications in TAP2‐deficient patients , 2004, European journal of immunology.

[238]  J. Berman,et al.  Shedding of PECAM‐1 during HIV infection: a potential role for soluble PECAM‐1 in the pathogenesis of NeuroAIDS , 2006, Journal of leukocyte biology.

[239]  B. de Strooper,et al.  Cell–matrix interaction via CD44 is independently regulated by different metalloproteinases activated in response to extracellular Ca2+ influx and PKC activation , 2004, The Journal of cell biology.

[240]  H. Ackermann,et al.  sE-cadherin serves as a diagnostic and predictive parameter in prostate cancer patients , 2015, Journal of Experimental & Clinical Cancer Research.

[241]  G. Calothy,et al.  The noncatalytic TrkCNC2 receptor is cleaved by metalloproteases upon neurotrophin-3 stimulation , 2003, Oncogene.

[242]  C. Blobel,et al.  Stimulation of Platelet-derived Growth Factor Receptor β (PDGFRβ) Activates ADAM17 and Promotes Metalloproteinase-dependent Cross-talk between the PDGFRβ and Epidermal Growth Factor Receptor (EGFR) Signaling Pathways* , 2010, The Journal of Biological Chemistry.

[243]  D. Kingsley,et al.  Use of a mutant cell line to study the kinetics and function of O-linked glycosylation of low density lipoprotein receptors. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[244]  Zemin Zhang,et al.  Signal peptide prediction based on analysis of experimentally verified cleavage sites , 2004, Protein science : a publication of the Protein Society.

[245]  C Collins,et al.  Insulin‐like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. , 1986, The EMBO journal.

[246]  R. Black,et al.  Unaltered Cleavage and Secretion of Angiotensin-converting Enzyme in Tumor Necrosis Factor-α-converting Enzyme-deficient Mice* , 1999, The Journal of Biological Chemistry.

[247]  A. Nusrat,et al.  Inflammation-induced desmoglein-2 ectodomain shedding compromises the mucosal barrier , 2015, Molecular biology of the cell.

[248]  O. De Wever,et al.  Soluble N‐cadherin in human biological fluids , 2006, International journal of cancer.

[249]  Pavel Montes de Oca-B.  Ectdomain shedding and regulated intracellular proteolysis in the central nervous system. , 2010, Central nervous system agents in medicinal chemistry.

[250]  S. Coughlin,et al.  Regulated Shedding of PAR1 N-terminal Exodomain from Endothelial Cells* , 2004, Journal of Biological Chemistry.

[251]  F. Koning,et al.  Human dendritic cells shed a functional, soluble form of the mannose receptor. , 1999, International immunology.

[252]  S. Nagata,et al.  Membrane-anchored CD40 is processed by the tumor necrosis factor-alpha-converting enzyme. Implications for CD40 signaling. , 2003, The Journal of biological chemistry.

[253]  N. Matsuki,et al.  Activity-Dependent Proteolytic Cleavage of Neuroligin-1 , 2012, Neuron.

[254]  R. Ward,et al.  Detection of a Soluble Form of the Leukocyte Surface Antigen CD48 in Plasma and Its Elevation in Patients with Lymphoid Leukemias and Arthritis , 2004, Journal of Clinical Immunology.

[255]  K. Gevaert,et al.  Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides , 2003, Nature Biotechnology.

[256]  Mamoun Ahram,et al.  Identification of shed proteins from chinese hamster ovary cells: Application of statistical confidence using human and mouse protein databases , 2005, Proteomics.

[257]  A. Buonanno,et al.  A negative feedback loop controls NMDA receptor function in cortical interneurons via neuregulin 2/ErbB4 signalling , 2015, Nature Communications.

[258]  Y. Okada,et al.  Soluble vascular adhesion protein-1 accumulates in proliferative diabetic retinopathy. , 2012, Investigative ophthalmology & visual science.

[259]  A. Kania,et al.  EphA4 Receptor Shedding Regulates Spinal Motor Axon Guidance , 2014, Current Biology.

[260]  U. Schepers,et al.  Secretome protein enrichment identifies physiological BACE1 protease substrates in neurons , 2012, The EMBO journal.

[261]  A. Henn,et al.  Preclinical Characterization of AMG 330, a CD3/CD33-Bispecific T-Cell–Engaging Antibody with Potential for Treatment of Acute Myelogenous Leukemia , 2014, Molecular Cancer Therapeutics.

[262]  A. Ludwig,et al.  The good, the bad and the ugly substrates for ADAM10 and ADAM17 in brain pathology, inflammation and cancer. , 2009, Seminars in cell & developmental biology.

[263]  G. Kolle,et al.  CRIM1 Regulates the Rate of Processing and Delivery of Bone Morphogenetic Proteins to the Cell Surface* , 2003, Journal of Biological Chemistry.

[264]  A. Fournier,et al.  IgLON Cell Adhesion Molecules Are Shed from the Cell Surface of Cortical Neurons to Promote Neuronal Growth* , 2014, The Journal of Biological Chemistry.

[265]  P. Crocker,et al.  Analysis of the CD33-related siglec family reveals that Siglec-9 is an endocytic receptor expressed on subsets of acute myeloid leukemia cells and absent from normal hematopoietic progenitors. , 2007, Leukemia research.

[266]  S. Moestrup,et al.  Tumor necrosis factor -converting enzyme (TACE/ADAM17) mediates ectodomain shedding of the scavenger receptor CD163 , 2010 .

[267]  Pavel Montes de Oca-B.  Ectodomain Shedding and Regulated Intracellular Proteolysis in the Central Nervous System , 2010 .

[268]  J. Bartles,et al.  Endoproteolytic cleavage in the extracellular domain of the integral plasma membrane protein CE9 precedes its redistribution from the posterior to the anterior tail of the rat spermatozoon during epididymal maturation [published erratum appears in J Cell Biol 1991 Nov;115(3):following 880] , 1991, The Journal of cell biology.

[269]  C. Blobel,et al.  Tumor Necrosis Factor-α Converting Enzyme/ADAM 17 Mediates MUC1 Shedding* , 2003, The Journal of Biological Chemistry.

[270]  Florian Steinberg,et al.  The FGFRL1 Receptor Is Shed from Cell Membranes, Binds Fibroblast Growth Factors (FGFs), and Antagonizes FGF Signaling in Xenopus Embryos* , 2009, The Journal of Biological Chemistry.

[271]  S. Estus,et al.  LRP1 shedding in human brain: roles of ADAM10 and ADAM17 , 2009, Molecular Neurodegeneration.

[272]  J. Scheller,et al.  Soluble T cell immunoglobulin and mucin domain (TIM)-1 and -4 generated by A Disintegrin And Metalloprotease (ADAM)-10 and -17 bind to phosphatidylserine. , 2014, Biochimica et biophysica acta.

[273]  R. Khokha,et al.  Cytokine stimulated vascular cell adhesion molecule-1 (VCAM-1) ectodomain release is regulated by TIMP-3. , 2005, Cardiovascular research.

[274]  D. Rader,et al.  A systematic study of modulation of ADAM-mediated ectodomain shedding by site-specific O-glycosylation , 2015, Proceedings of the National Academy of Sciences.

[275]  P. Altevogt,et al.  Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins , 2001, The Journal of cell biology.

[276]  K. Horiuchi,et al.  Cell Surface Colony-Stimulating Factor 1 Can Be Cleaved by TNF-α Converting Enzyme or Endocytosed in a Clathrin-Dependent Manner1 , 2007, The Journal of Immunology.

[277]  C. Degnin,et al.  Ligand activation leads to regulated intramembrane proteolysis of fibroblast growth factor receptor 3 , 2011, Molecular biology of the cell.

[278]  Andre T Baron,et al.  Shedding of soluble epidermal growth factor receptor (sEGFR) is mediated by a metalloprotease/fibronectin/integrin axis and inhibited by cetuximab. , 2013, Biochemistry.

[279]  T. Schöneberg,et al.  The Fate of Desmosomal Proteins in Apoptotic Cells* , 2001, The Journal of Biological Chemistry.

[280]  The Uniprot Consortium,et al.  UniProt: a hub for protein information , 2014, Nucleic Acids Res..

[281]  D. Spaner,et al.  Ectodomain shedding of CD200 from the B-CLL cell surface is regulated by ADAM28 expression. , 2013, Leukemia research.

[282]  A Cumano,et al.  A novel proteolytic cleavage involved in Notch signaling: the role of the disintegrin-metalloprotease TACE. , 2000, Molecular cell.

[283]  T. Nakamura,et al.  Purification and characterization of hepatocyte growth factor (HGF)-converting enzyme: activation of pro-HGF. , 1994, Biochemical and biophysical research communications.

[284]  Alex Y Strongin,et al.  An Alternative Processing of Integrin αv Subunit in Tumor Cells by Membrane Type-1 Matrix Metalloproteinase* , 2002, The Journal of Biological Chemistry.

[285]  Voltage-gated Na+ channels: potential for beta subunits as therapeutic targets. , 2008, Expert opinion on therapeutic targets.

[286]  G. Weskamp,et al.  Evidence for a Critical Role of the Tumor Necrosis Factor α Convertase (TACE) in Ectodomain Shedding of the p75 Neurotrophin Receptor (p75NTR)* , 2004, Journal of Biological Chemistry.

[287]  B. Lu,et al.  Soluble CD276 (B7‐H3) is released from monocytes, dendritic cells and activated T cells and is detectable in normal human serum , 2008, Immunology.

[288]  S. Hanash,et al.  Proteomic Analysis of Ovarian Cancer Cells Reveals Dynamic Processes of Protein Secretion and Shedding of Extra-Cellular Domains , 2008, PloS one.

[289]  Biao Xu,et al.  Syndecan-4 shedding is involved in the oxidative stress and inflammatory responses in left atrial tissue with valvular atrial fibrillation. , 2015, International journal of clinical and experimental pathology.

[290]  Y. Ganor,et al.  TCR Activation Eliminates Glutamate Receptor GluR3 from the Cell Surface of Normal Human T Cells, via an Autocrine/Paracrine Granzyme B-Mediated Proteolytic Cleavage , 2007, The Journal of Immunology.

[291]  R. Zager,et al.  Toll-like receptor (TLR4) shedding and depletion: acute proximal tubular cell responses to hypoxic and toxic injury. , 2007, American journal of physiology. Renal physiology.

[292]  H. Verspaget,et al.  Matrix metalloproteinase-14 (MT1-MMP)-mediated endoglin shedding inhibits tumor angiogenesis. , 2010, Cancer research.

[293]  T. Akiyama,et al.  DREG, a developmentally regulated G protein‐coupled receptor containing two conserved proteolytic cleavage sites , 2004, Genes to cells : devoted to molecular & cellular mechanisms.

[294]  Sarah Boyd,et al.  PMAP: databases for analyzing proteolytic events and pathways , 2008, Nucleic Acids Res..

[295]  Nancy Argüelles,et al.  Author ' s , 2008 .

[296]  S. Kuruppu,et al.  Characterisation of endothelin converting enzyme‐1 shedding from endothelial cells , 2007, FEBS letters.

[297]  J. Peschon,et al.  TNF-α-Converting Enzyme Cleaves the Macrophage Colony-Stimulating Factor Receptor in Macrophages Undergoing Activation1 , 2001, The Journal of Immunology.

[298]  H. Jockusch,et al.  The Metalloprotease Disintegrin ADAM8 , 2002, The Journal of Biological Chemistry.

[299]  J. Bonnefoy,et al.  Soluble CD86 is a costimulatory molecule for human T lymphocytes. , 2000, Immunity.

[300]  J. Scheller,et al.  Human and Murine Interleukin 23 Receptors Are Novel Substrates for A Disintegrin and Metalloproteases ADAM10 and ADAM17* , 2016, The Journal of Biological Chemistry.

[301]  H. Federoff,et al.  Ectodomain shedding of nectin‐1 regulates the maintenance of dendritic spine density , 2012, Journal of neurochemistry.

[302]  D. Golenbock,et al.  Metalloproteinase-Dependent TLR2 Ectodomain Shedding is Involved in Soluble Toll-Like Receptor 2 (sTLR2) Production , 2014, PloS one.

[303]  A. Nusrat,et al.  Cleavage of transmembrane junction proteins and their role in regulating epithelial homeostasis , 2013, Tissue barriers.

[304]  K. Miyake,et al.  Roles of the Cleaved N-Terminal TLR3 Fragment and Cell Surface TLR3 in Double-Stranded RNA Sensing , 2014, The Journal of Immunology.

[305]  N. Clarke,et al.  Angiogenesis , Metastasis , and the Cellular Microenvironment Copper Modulates Zinc Metalloproteinase-Dependent Ectodomain Shedding of Key Signaling and Adhesion Proteins and Promotes the Invasion of Prostate Cancer Epithelial Cells , 2012 .

[306]  R. Leduc,et al.  Proteolysis-induced N-terminal Ectodomain Shedding of the Integral Membrane Glycoprotein CUB Domain-containing Protein 1 (CDCP1) Is Accompanied by Tyrosine Phosphorylation of Its C-terminal Domain and Recruitment of Src and PKCδ* , 2010, The Journal of Biological Chemistry.

[307]  I. Stamenkovic,et al.  Matrix metalloproteinase-7-mediated cleavage of Fas ligand protects tumor cells from chemotherapeutic drug cytotoxicity. , 2001, Cancer research.

[308]  Akhilesh Pandey,et al.  Human Protein Reference Database and Human Proteinpedia as discovery tools for systems biology. , 2009, Methods in molecular biology.

[309]  D. Hoekstra,et al.  The function of neurofascin155 in oligodendrocytes is regulated by metalloprotease-mediated cleavage and ectodomain shedding. , 2006, Experimental cell research.

[310]  L. Lum,et al.  Evidence for a role of a tumor necrosis factor-alpha (TNF-alpha)-converting enzyme-like protease in shedding of TRANCE, a TNF family member involved in osteoclastogenesis and dendritic cell survival. , 1999, The Journal of biological chemistry.

[311]  C. Chitambar,et al.  Release of soluble transferrin receptor from the surface of human leukemic HL60 cells. , 1989, Blood.

[312]  H. Aburatani,et al.  Identification of ROBO1 as a Novel Hepatocellular Carcinoma Antigen and a Potential Therapeutic and Diagnostic Target , 2006, Clinical Cancer Research.

[313]  U. Sen,et al.  Tumor Necrosis Factor-α-converting Enzyme (TACE/ADAM-17) Mediates the Ectodomain Cleavage of Intercellular Adhesion Molecule-1 (ICAM-1)* , 2006, Journal of Biological Chemistry.

[314]  Kiyoko Kato,et al.  A Disintegrin and Metalloproteinase 9 Is Involved in Ectodomain Shedding of Receptor-Binding Cancer Antigen Expressed on SiSo Cells , 2014, BioMed research international.

[315]  J. Joyce,et al.  Pericellular proteolysis in cancer , 2014, Genes & development.

[316]  H. Sul,et al.  Ectodomain Shedding of Preadipocyte Factor 1 (Pref-1) by Tumor Necrosis Factor Alpha Converting Enzyme (TACE) and Inhibition of Adipocyte Differentiation , 2006, Molecular and Cellular Biology.

[317]  D. Carey,et al.  Secreted gliomedin is a perinodal matrix component of peripheral nerves , 2007, The Journal of cell biology.

[318]  P. Noy,et al.  Sprouting angiogenesis is regulated by shedding of the C‐type lectin family 14, member A (CLEC14A) ectodomain, catalyzed by rhomboid‐like 2 protein (RHBDL2) , 2016, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[319]  C. B. Alexander,et al.  Loss of fibroblast Thy-1 expression correlates with lung fibrogenesis. , 2005, The American journal of pathology.

[320]  P. Park,et al.  Molecular and Cellular Mechanisms of Ectodomain Shedding , 2010, Anatomical record.

[321]  P. Saftig,et al.  Klotho is a substrate for alpha-, beta- and gamma-secretase. , 2009, FEBS letters.

[322]  P. Dempsey,et al.  ADAMs as mediators of EGF receptor transactivation by G protein-coupled receptors. , 2006, American journal of physiology. Cell physiology.

[323]  R. Hughey,et al.  Proteolytic Processing of the Epithelial Sodium Channel γ Subunit Has a Dominant Role in Channel Activation* , 2008, Journal of Biological Chemistry.

[324]  S. Thorne,et al.  Modulation of NKG2D-ligand Cell Surface Expression Enhances Immune Cell Therapy of Cancer , 2011, Journal of immunotherapy.

[325]  C. Blobel,et al.  Critical function for ADAM9 in mouse prostate cancer. , 2005, Cancer research.

[326]  W. Tien,et al.  SecretePipe: a screening pipeline for secreted proteins with competence to identify potential membrane-bound shed markers. , 2013, Journal of proteome research.

[327]  G. Rebeck,et al.  Regulation of ApoE receptor proteolysis by ligand binding. , 2005, Brain research. Molecular brain research.

[328]  P. Comoglio,et al.  Functional Regulation of Semaphorin Receptors by Proprotein Convertases* , 2003, The Journal of Biological Chemistry.

[329]  Felipe García,et al.  Metalloproteinases Shed TREM-1 Ectodomain from Lipopolysaccharide-Stimulated Human Monocytes1 , 2007, The Journal of Immunology.

[330]  D. Hallahan,et al.  TNF-α and IL-1 Upregulate Membrane-Bound and Soluble E-Selectin through a Common Pathway , 1997 .

[331]  C. Dingwall,et al.  Prodomain Processing of Asp1 (BACE2) Is Autocatalytic* , 2001, The Journal of Biological Chemistry.

[332]  M. Stack,et al.  Membrane-type I matrix metalloproteinase-dependent ectodomain shedding of mucin16/ CA-125 on ovarian cancer cells modulates adhesion and invasion of peritoneal mesothelium , 2014, Biological chemistry.

[333]  Steffen B. E. Wolff,et al.  mGluR1/5-Dependent Long-Term Depression Requires the Regulated Ectodomain Cleavage of Neuronal Pentraxin NPR by TACE , 2008, Neuron.

[334]  P. Dubreuil,et al.  Nectin-4, a New Serological Breast Cancer Marker, Is a Substrate for Tumor Necrosis Factor-α-converting Enzyme (TACE)/ADAM-17* , 2005, Journal of Biological Chemistry.

[335]  J. Blusztajn,et al.  Collagen type I selectively activates ectodomain shedding of the discoidin domain receptor 1: Involvement of Src tyrosine kinase , 2006, Journal of cellular biochemistry.

[336]  S. Gordon,et al.  Proteolytic cleavage of the EMR2 receptor requires both the extracellular stalk and the GPS motif , 2003, FEBS letters.

[337]  Takeshi Kimura,et al.  Serum Soluble Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Levels Are Elevated in Acute Coronary Syndrome: A Novel Marker for Early Diagnosis , 2005, Circulation.

[338]  J. Ulvila,et al.  β-Adrenergic Agonists Mediate Enhancement of β1-Adrenergic Receptor N-terminal Cleavage and Stabilization In Vivo and In Vitro , 2013, Molecular Pharmacology.

[339]  G. Eisenhofer,et al.  Reducing agents induce thrombomodulin shedding in human endothelial cells. , 2010, Thrombosis research.

[340]  J. Strominger,et al.  CD43, the major sialoglycoprotein of human leukocytes, is proteolytically cleaved from the surface of stimulated lymphocytes and granulocytes. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[341]  G. Camussi,et al.  Preeclamptic sera induce nephrin shedding from podocytes through endothelin-1 release by endothelial glomerular cells. , 2008, American journal of physiology. Renal physiology.

[342]  P. Saftig,et al.  Regulated ADAM10-dependent Ectodomain Shedding of γ-Protocadherin C3 Modulates Cell-Cell Adhesion* , 2006, Journal of Biological Chemistry.

[343]  J. Fawcett,et al.  Two separate metalloproteinase activities are responsible for the shedding and processing of the NG2 proteoglycan in vitro , 2005, Molecular and Cellular Neuroscience.

[344]  M. Schachner,et al.  Ectodomain Shedding of the Neural Recognition Molecule CHL1 by the Metalloprotease-disintegrin ADAM8 Promotes Neurite Outgrowth and Suppresses Neuronal Cell Death* , 2004, Journal of Biological Chemistry.

[345]  M. Marzolo,et al.  Neurotrophins regulate ApoER2 proteolysis through activation of the Trk signaling pathway , 2014, BMC Neuroscience.

[346]  Masayuki Shimoda,et al.  ADAM28 is activated by MMP-7 (matrilysin-1) and cleaves insulin-like growth factor binding protein-3. , 2004, Biochemical and biophysical research communications.

[347]  Y. Nakanuma,et al.  GI24 enhances tumor invasiveness by regulating cell surface membrane‐type 1 matrix metalloproteinase , 2010, Cancer science.

[348]  T. Sasazuki,et al.  Modulation of TNF-α-converting enzyme by the spike protein of SARS-CoV and ACE2 induces TNF-α production and facilitates viral entry , 2008, Proceedings of the National Academy of Sciences.

[349]  P. Glynn,et al.  A novel metalloproteinase associated with brain myelin membranes. Isolation and characterization. , 1989, The Journal of biological chemistry.

[350]  J. Kiss,et al.  Secretion of VEGF-165 has unique characteristics, including shedding from the plasma membrane , 2014, Molecular biology of the cell.

[351]  S. Russell,et al.  Specific inhibition of ectodomain shedding of glycoprotein Ibα by targeting its juxtamembrane shedding cleavage site , 2013, Journal of thrombosis and haemostasis : JTH.

[352]  H. Krell,et al.  The Extracellular N Terminus of the Endothelin B (ETB) Receptor Is Cleaved by a Metalloprotease in an Agonist-dependent Process* , 2002, The Journal of Biological Chemistry.

[353]  K. Gevaert,et al.  Caspase-specific and nonspecific in vivo protein processing during Fas-induced apoptosis , 2005, Nature Methods.

[354]  Neil D. Rawlings,et al.  Twenty years of the MEROPS database of proteolytic enzymes, their substrates and inhibitors , 2015, Nucleic Acids Res..

[355]  C. Lagenaur,et al.  The Murine P84 Neural Adhesion Molecule Is SHPS-1, a Member of the Phosphatase-Binding Protein Family , 1997, The Journal of Neuroscience.

[356]  Jingjing Jiang,et al.  Ectodomain Shedding and Autocleavage of the Cardiac Membrane Protease Corin* , 2010, The Journal of Biological Chemistry.

[357]  Anthony P. Monaco,et al.  The Dyslexia-associated KIAA0319 Protein Undergoes Proteolytic Processing with γ-Secretase-independent Intramembrane Cleavage , 2010, The Journal of Biological Chemistry.

[358]  Katsumi Miyauchi,et al.  Circulating soluble LR11, a novel marker of smooth muscle cell proliferation, is enhanced after coronary stenting in response to vascular injury. , 2014, Atherosclerosis.

[359]  Y. Ba,et al.  Shed Syndecan-1 is involved in chemotherapy resistance via the EGFR pathway in colorectal cancer , 2014, British Journal of Cancer.

[360]  T. Tahir,et al.  Regulated Proteolytic Processing of Tie1 Modulates Ligand Responsiveness of the Receptor-tyrosine Kinase Tie2* , 2007, Journal of Biological Chemistry.

[361]  M. Letarte,et al.  Primary structure of endoglin, an RGD-containing glycoprotein of human endothelial cells. , 1990, The Journal of biological chemistry.

[362]  H. Rammensee,et al.  Tumor-associated MICA is shed by ADAM proteases. , 2008, Cancer research.

[363]  R. Gerli,et al.  In rheumatoid arthritis soluble CD30 ligand is present at high levels and induces apoptosis of CD30(+)T cells. , 2014, Immunology letters.

[364]  G. Strous.  Golgi and secreted galactosyltransferase. , 1986, CRC critical reviews in biochemistry.

[365]  María Martín,et al.  UniProt: A hub for protein information , 2015 .

[366]  K. Horiuchi,et al.  Receptor Activator of NF-κB (RANK) Ligand Induces Ectodomain Shedding of RANK in Murine RAW264.7 Macrophages , 2010, The Journal of Immunology.

[367]  B. Strooper,et al.  The disintegrins ADAM10 and TACE contribute to the constitutive and phorbol ester-regulated normal cleavage of the cellular prion protein. , 2001, The Journal of biological chemistry.

[368]  B. de Strooper,et al.  β Subunits of Voltage-gated Sodium Channels Are Novel Substrates of β-Site Amyloid Precursor Protein-cleaving Enzyme (BACE1) and γ-Secretase* , 2005, Journal of Biological Chemistry.

[369]  H. Shimizu,et al.  Metalloproteinase- and γ-Secretase-mediated Cleavage of Protein-tyrosine Phosphatase Receptor Type Z* , 2008, Journal of Biological Chemistry.

[370]  H. Verheul,et al.  Soluble aminopeptidase N/CD13 in malignant and nonmalignant effusions and intratumoral fluid. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[371]  B. de Strooper,et al.  The Cell Adhesion Protein P-selectin Glycoprotein Ligand-1 Is a Substrate for the Aspartyl Protease BACE1* , 2003, Journal of Biological Chemistry.

[372]  Katrin Eichelbaum,et al.  Rapid Temporal Dynamics of Transcription, Protein Synthesis, and Secretion during Macrophage Activation* , 2014, Molecular & Cellular Proteomics.

[373]  N. Hooper,et al.  Tumor Necrosis Factor-α Convertase (ADAM17) Mediates Regulated Ectodomain Shedding of the Severe-acute Respiratory Syndrome-Coronavirus (SARS-CoV) Receptor, Angiotensin-converting Enzyme-2 (ACE2) , 2005, Journal of Biological Chemistry.

[374]  Y. Kadono,et al.  Negative Regulation of Osteoclastogenesis by Ectodomain Shedding of Receptor Activator of NF-κB Ligand* , 2006, Journal of Biological Chemistry.

[375]  D. Strickland,et al.  γ-Secretase-mediated Release of the Low Density Lipoprotein Receptor-related Protein 1B Intracellular Domain Suppresses Anchorage-independent Growth of Neuroglioma Cells* , 2007, Journal of Biological Chemistry.

[376]  Y. Okada,et al.  VIP36 Protein Is a Target of Ectodomain Shedding and Regulates Phagocytosis in Macrophage Raw 264.7 Cells* , 2011, The Journal of Biological Chemistry.

[377]  K. Miyazaki,et al.  Matrilysin (matrix metalloprotease‐7) cleaves membrane‐bound annexin II and enhances binding of tissue‐type plasminogen activator to cancer cell surfaces , 2008, The FEBS journal.

[378]  M. Scheinfeld,et al.  Processing of beta-amyloid precursor-like protein-1 and -2 by gamma-secretase regulates transcription. , 2002, The Journal of biological chemistry.

[379]  R. Nagle,et al.  INTEGRIN α6 CLEAVAGE: A NOVEL MODIFICATION TO MODULATE CELL MIGRATION , 2007 .

[380]  L. Biancone,et al.  In vivo modulation of CD26 (dipeptidyl peptidase IV) in the mouse: effects of polyreactive and monoreactive antibodies. , 1996, Transplantation.

[381]  S. V. van Deventer,et al.  Abrogation of IFN-gamma mediated epithelial barrier disruption by serine protease inhibition. , 2005, Clinical and experimental immunology.

[382]  C. Blobel,et al.  Tumor necrosis factor-alpha converting enzyme/ADAM 17 mediates MUC1 shedding. , 2003, The Journal of biological chemistry.

[383]  Sarah E. Ewald,et al.  The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor , 2008, Nature.

[384]  S. Gordon,et al.  A Functional Soluble Form of the Murine Mannose Receptor Is Produced by Macrophages in Vitro and Is Present in Mouse Serum* , 1998, The Journal of Biological Chemistry.

[385]  M. Hellwig,et al.  Soluble Human Interleukin–4 Receptor Is Produced by Activated T Cells under the Control of Metalloproteinases , 1999, International Archives of Allergy and Immunology.

[386]  J. Waltenberger,et al.  A Disintegrin and Metalloprotease 10 Is a Novel Mediator of Vascular Endothelial Growth Factor–Induced Endothelial Cell Function in Angiogenesis and Is Associated With Atherosclerosis , 2010, Arteriosclerosis, thrombosis, and vascular biology.

[387]  S. Levy,et al.  Spontaneous release of the Leu-2 (T8) molecule from human T cells , 1983, The Journal of experimental medicine.

[388]  S. Rose-John,et al.  The SLAM family member CD84 is regulated by ADAM10 and calpain in platelets , 2012, Journal of thrombosis and haemostasis : JTH.

[389]  S. Bohlson,et al.  CD93 Is Rapidly Shed from the Surface of Human Myeloid Cells and the Soluble Form Is Detected in Human Plasma1 , 2005, The Journal of Immunology.

[390]  Erwin G. Van Meir,et al.  A proprotein convertase/MMP-14 proteolytic cascade releases a novel 40 kDa vasculostatin from tumor suppressor BAI1 , 2012, Oncogene.

[391]  B. Zlokovic,et al.  Shedding of soluble platelet-derived growth factor receptor-β from human brain pericytes , 2015, Neuroscience Letters.

[392]  T. Kang,et al.  Autolytic Processing at Glu586-Ser587within the Cysteine-rich Domain of Human Adamalysin 19/Disintegrin-Metalloproteinase 19 Is Necessary for Its Proteolytic Activity* , 2002, The Journal of Biological Chemistry.

[393]  P. Distefano,et al.  Released form of CNTF receptor alpha component as a soluble mediator of CNTF responses. , 1993, Science.

[394]  Chungho Kim,et al.  Shedding of epithin/PRSS14 is induced by TGF-β and mediated by tumor necrosis factor-α converting enzyme. , 2014, Biochemical and biophysical research communications.

[395]  G. Yancopoulos,et al.  Soluble forms of the interleukin-6 signal-transducing receptor component gp130 in human serum possessing a potential to inhibit signals through membrane-anchored gp130. , 1993, Blood.

[396]  Y. Matsuzawa,et al.  Ectodomain Shedding of Epidermal Growth Factor Receptor Ligands Is Required for Keratinocyte Migration in Cutaneous Wound Healing , 2000, The Journal of cell biology.

[397]  K. Hirata,et al.  Soluble Lutheran/basal cell adhesion molecule is detectable in plasma of hepatocellular carcinoma patients and modulates cellular interaction with laminin-511 in vitro. , 2014, Experimental cell research.

[398]  S. Fukuoka,et al.  Analysis of the C-terminal structure of urinary Tamm-Horsfall protein reveals that the release of the glycosyl phosphatidylinositol-anchored counterpart from the kidney occurs by phenylalanine-specific proteolysis. , 2001, Biochemical and biophysical research communications.

[399]  Mitchell Ho,et al.  Megakaryocyte Potentiation Factor Cleaved from Mesothelin Precursor Is a Useful Tumor Marker in the Serum of Patients with Mesothelioma , 2006, Clinical Cancer Research.

[400]  D. Benos,et al.  Proteolytic Cleavage of Human Acid-sensing Ion Channel 1 by the Serine Protease Matriptase* , 2010, The Journal of Biological Chemistry.

[401]  R. Sedláček,et al.  ADAM10/17-dependent release of soluble c-Met correlates with hepatocellular damage. , 2013, Folia biologica.

[402]  G. Gorodeski,et al.  Estrogen abrogates transcervical tight junctional resistance by acceleration of occludin modulation. , 2004, The Journal of clinical endocrinology and metabolism.

[403]  B. Peers,et al.  Processing by proprotein convertases is required for glypican-3 modulation of cell survival, Wnt signaling, and gastrulation movements , 2003, The Journal of cell biology.

[404]  Steven P. Gygi,et al.  Identification of β-Secretase (BACE1) Substrates Using Quantitative Proteomics , 2009, PloS one.

[405]  P. Feng,et al.  N-Glycosylation Is Required for Matriptase-2 Autoactivation and Ectodomain Shedding* , 2014, The Journal of Biological Chemistry.

[406]  P. Koolwijk,et al.  metalloproteinase-12: implication for angiogenesis in fibrin matrices Proteolysis of the urokinase-type plasminogen activator receptor by , 2013 .

[407]  K. Miyazaki,et al.  Matrilysin (MMP‐7) cleaves C‐type lectin domain family 3 member A (CLEC3A) on tumor cell surface and modulates its cell adhesion activity , 2009, Journal of cellular biochemistry.

[408]  C. Masters,et al.  Human amyloid precursor-like protein 1--cDNA cloning, ectopic expression in COS-7 cells and identification of soluble forms in the cerebrospinal fluid. , 1997, European journal of biochemistry.

[409]  J. Ling,et al.  Wound-induced HB-EGF ectodomain shedding and EGFR activation in corneal epithelial cells. , 2004, Investigative ophthalmology & visual science.

[410]  M. Krieger,et al.  Effects of O-linked glycosylation on the cell surface expression and stability of decay-accelerating factor, a glycophospholipid-anchored membrane protein. , 1989, The Journal of biological chemistry.

[411]  M. Stoffel,et al.  Tmem27 dimerization, deglycosylation, plasma membrane depletion, and the extracellular Phe-Phe motif are negative regulators of cleavage by Bace2 , 2012, Biological chemistry.

[412]  Kai Lin,et al.  Ephrin-B2-induced Cleavage of EphB2 Receptor Is Mediated by Matrix Metalloproteinases to Trigger Cell Repulsion* , 2008, Journal of Biological Chemistry.

[413]  Nicholas A. Hamilton,et al.  LOCATE: a mammalian protein subcellular localization database , 2007, Nucleic Acids Res..

[414]  A. Mantovani,et al.  M‐CSF induces the expression of a membrane‐bound form of IL‐18 in a subset of human monocytes differentiating in vitro toward macrophages , 2012, European journal of immunology.

[415]  Asif Ahmed,et al.  VEGF Induces Tie2 Shedding via a Phosphoinositide 3-Kinase/Akt–Dependent Pathway to Modulate Tie2 Signaling , 2007, Arteriosclerosis, thrombosis, and vascular biology.

[416]  M. Hebbar,et al.  Detection of circulating soluble CD28 in patients with systemic lupus erythematosus, primary Sjögren's syndrome and systemic sclerosis , 2004, Clinical and experimental immunology.

[417]  A. Moreau,et al.  Expression and Release of HLA-E by Melanoma Cells and Melanocytes: Potential Impact on the Response of Cytotoxic Effector Cells1 , 2006, The Journal of Immunology.

[418]  M. Götz,et al.  An Emerging Role of Sonic Hedgehog Shedding as a Modulator of Heparan Sulfate Interactions* , 2012, The Journal of Biological Chemistry.

[419]  J. Schifferli,et al.  Soluble complement receptor type 1 (CD35) is released from leukocytes by surface cleavage , 1994, European journal of immunology.

[420]  C. Lacombe,et al.  Regulation of cell surface transferrin receptor-2 by iron-dependent cleavage and release of a soluble form , 2015, Haematologica.

[421]  V. Hearing,et al.  Glycoprotein nonmetastatic melanoma protein b, a melanocytic cell marker, is a melanosome‐specific and proteolytically released protein , 2010, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[422]  S. M. Park,et al.  Proteolytic Cleavage of Extracellular Secreted α-Synuclein via Matrix Metalloproteinases* , 2005, Journal of Biological Chemistry.

[423]  P. Sonderegger,et al.  Calsyntenin-1, a Proteolytically Processed Postsynaptic Membrane Protein with a Cytoplasmic Calcium-Binding Domain , 2001, Molecular and Cellular Neuroscience.

[424]  J. Arribas,et al.  ADAM17 (TACE) regulates TGFβ signaling through the cleavage of vasorin , 2011, Oncogene.

[425]  R. Hubert,et al.  Catalytic cleavage of the androgen-regulated TMPRSS2 protease results in its secretion by prostate and prostate cancer epithelia. , 2001, Cancer research.

[426]  E. Thorsby,et al.  Interferon-gamma enhances expression of secretory component, the epithelial receptor for polymeric immunoglobulins. , 1987, Journal of immunology.

[427]  S. Meri,et al.  Shedding and enrichment of the glycolipid-anchored complement lysis inhibitor protectin (CD59) into milk fat globules. , 1995, Immunology.

[428]  P. Altevogt,et al.  Metalloprotease-mediated tumor cell shedding of B7-H6, the ligand of the natural killer cell-activating receptor NKp30. , 2014, Cancer research.

[429]  J. Filmus,et al.  Glypican-3 as a serum marker for hepatocellular carcinoma. , 2005, Cancer research.

[430]  J. Nathans,et al.  Proteolytic Shedding of the Extracellular Domain of Photoreceptor Cadherin , 2004, Journal of Biological Chemistry.

[431]  T. Golde,et al.  Identification of ligand-induced proteolytic cleavage and ectodomain shedding of VEGFR-1/FLT1 in leukemic cancer cells. , 2009, Cancer research.

[432]  Brigitte Mack,et al.  Nuclear signalling by tumour-associated antigen EpCAM , 2009, Nature Cell Biology.

[433]  Vera Knaüper,et al.  Phorbol Ester-induced Shedding of the Prostate Cancer Marker Transmembrane Protein with Epidermal Growth Factor and Two Follistatin Motifs 2 Is Mediated by the Disintegrin and Metalloproteinase-17* , 2007, Journal of Biological Chemistry.

[434]  R. Seruca,et al.  Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells , 2010, Oncogene.

[435]  S. Jalkanen,et al.  Differential Regulation and Function of CD73, a Glycosyl-Phosphatidylinositol–linked 70-kD Adhesion Molecule, on Lymphocytes and Endothelial Cells , 1997, The Journal of cell biology.

[436]  B. de Strooper,et al.  Syndecan 3 Intramembrane Proteolysis Is Presenilin/γ-Secretase-dependent and Modulates Cytosolic Signaling* , 2003, Journal of Biological Chemistry.

[437]  A. Krüger,et al.  Tissue inhibitor of metalloproteinases-1 promotes liver metastasis by induction of hepatocyte growth factor signaling. , 2007, Cancer research.

[438]  K. Syrigos,et al.  Soluble e-cadherin as a diagnostic and prognostic marker in gastric carcinoma , 2013, Folia medica.

[439]  P. Perrin,et al.  CD146 and its Soluble Form Regulate Monocyte Transendothelial Migration , 2009, Arteriosclerosis, thrombosis, and vascular biology.

[440]  Yusuke Nakamura,et al.  Crosstalk of EDA-A2/XEDAR in the p53 Signaling Pathway , 2010, Molecular Cancer Research.

[441]  S. Meri,et al.  Complement inhibitor membrane cofactor protein (MCP; CD46) is constitutively shed from cancer cell membranes in vesicles and converted by a metalloproteinase to a functionally active soluble form , 2004, European journal of immunology.

[442]  J. Kirsch,et al.  Activity-Dependent Shedding of the NMDA Receptor Glycine Binding Site by Matrix Metalloproteinase 3: A PUTATIVE Mechanism of Postsynaptic Plasticity , 2008, PloS one.

[443]  Eunjoon Kim,et al.  Long-term depression-inducing stimuli promote cleavage of the synaptic adhesion molecule NGL-3 through NMDA receptors, matrix metalloproteinases and presenilin/γ-secretase , 2014, Philosophical Transactions of the Royal Society B: Biological Sciences.

[444]  David C. Lee,et al.  Tumor Necrosis Factor-α Converting Enzyme (TACE) Regulates Epidermal Growth Factor Receptor Ligand Availability* , 2002, The Journal of Biological Chemistry.

[445]  P. Elwood,et al.  The conversion of the human membrane-associated folate binding protein (folate receptor) to the soluble folate binding protein by a membrane-associated metalloprotease. , 1991, The Journal of biological chemistry.

[446]  Ashok Kumar,et al.  IL-7 decreases IL-7 receptor alpha (CD127) expression and induces the shedding of CD127 by human CD8+ T cells. , 2007, International immunology.

[447]  R. Newton,et al.  ADAM17 cleaves CD16b (FcγRIIIb) in human neutrophils. , 2013, Biochimica et biophysica acta.

[448]  Takao Inoue,et al.  Increased Ectodomain Shedding of Cell Adhesion Molecule 1 from Pancreatic Islets in Type 2 Diabetic Pancreata: Correlation with Hemoglobin A1c Levels , 2014, PloS one.

[449]  G. Germino,et al.  Polyductin undergoes notch-like processing and regulated release from primary cilia. , 2007, Human molecular genetics.

[450]  J. Casal,et al.  An RGD Motif Present in Cadherin 17 Induces Integrin Activation and Tumor Growth* , 2014, The Journal of Biological Chemistry.

[451]  A. Ullrich,et al.  Distinct ADAM Metalloproteinases Regulate G Protein-coupled Receptor-induced Cell Proliferation and Survival* , 2004, Journal of Biological Chemistry.

[452]  R. Black,et al.  Tumor necrosis factor-alpha converting enzyme. , 2002, The international journal of biochemistry & cell biology.

[453]  M. Noda,et al.  Neuroglycan C, a Novel Membrane-spanning Chondroitin Sulfate Proteoglycan That Is Restricted to the Brain (*) , 1995, The Journal of Biological Chemistry.

[454]  C. Hoogenraad,et al.  Lrig2 Negatively Regulates Ectodomain Shedding of Axon Guidance Receptors by ADAM Proteases. , 2015, Developmental cell.

[455]  J. Massagué,et al.  Transforming growth factor-alpha and beta-amyloid precursor protein share a secretory mechanism , 1995, The Journal of cell biology.

[456]  W. Ouyang,et al.  Establishment of an ELISA system for determining soluble LAIR-1 levels in sera of patients with HFRS and kidney transplant. , 2004, Journal of immunological methods.

[457]  C. Leifer,et al.  Negative regulation of signaling by a soluble form of toll‐like receptor 9 , 2011, European journal of immunology.

[458]  H. Broihier,et al.  Crimpy enables discrimination of presynaptic and postsynaptic pools of a BMP at the Drosophila neuromuscular junction. , 2014, Developmental cell.

[459]  Hongkuan Yang,et al.  Soluble LRIG2 Ectodomain Is Released from Glioblastoma Cells and Promotes the Proliferation and Inhibits the Apoptosis of Glioblastoma Cells In Vitro and In Vivo in a Similar Manner to the Full-Length LRIG2 , 2014, PloS one.

[460]  M. Bidlingmaier,et al.  Generation of human soluble leptin receptor by proteolytic cleavage of membrane-anchored receptors. , 2001, Endocrinology.

[461]  B. Schaub,et al.  Transition of galactosyltransferase 1 from trans-Golgi cisterna to the trans-Golgi network is signal mediated. , 2006, Molecular biology of the cell.

[462]  E. Kojro,et al.  Ligand-induced Cleavage of the V2 Vasopressin Receptor by a Plasma Membrane Metalloproteinase (*) , 1995, The Journal of Biological Chemistry.

[463]  A. Steinle,et al.  Proteolytic release of soluble UL16-binding protein 2 from tumor cells. , 2006, Cancer research.

[464]  T. Yamashita,et al.  TACE cleaves neogenin to desensitize cortical neurons to the repulsive guidance molecule , 2011, Neuroscience Research.

[465]  A. Plet,et al.  Natural, Proteolytic Release of a Soluble Form of Human IL-15 Receptor α-Chain That Behaves as a Specific, High Affinity IL-15 Antagonist1 , 2004, The Journal of Immunology.

[466]  Ying Jin,et al.  Activity‐dependent cleavage of brain glutamic acid decarboxylase 65 by calpain , 2006, Journal of neurochemistry.

[467]  A. Dziki,et al.  Matrix Metalloproteinase-2 Cleavage of the β1 Integrin Ectodomain Facilitates Colon Cancer Cell Motility* , 2012, The Journal of Biological Chemistry.

[468]  Jeffrey W. Smith,et al.  A Residue in the S2 Subsite Controls Substrate Selectivity of Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9* , 2003, Journal of Biological Chemistry.

[469]  M. Scheinfeld,et al.  Processing of β-Amyloid Precursor-like Protein-1 and -2 by γ-Secretase Regulates Transcription* , 2002, The Journal of Biological Chemistry.

[470]  V. Tarabykin,et al.  FLRT2 and FLRT3 act as repulsive guidance cues for Unc5-positive neurons , 2011, Neuroscience Research.

[471]  J. Keski‐Oja,et al.  ADAM10-mediated Release of Complement Membrane Cofactor Protein during Apoptosis of Epithelial Cells* , 2006, Journal of Biological Chemistry.

[472]  C. Boudier,et al.  Cleavage of lymphocyte surface antigens CD2, CD4, and CD8 by polymorphonuclear leukocyte elastase and cathepsin G in patients with cystic fibrosis. , 1995, Journal of immunology.

[473]  K. Horiuchi,et al.  Different ADAMs have distinct influences on Kit ligand processing: phorbol-ester-stimulated ectodomain shedding of Kitl1 by ADAM17 is reduced by ADAM19 , 2007, Journal of Cell Science.

[474]  M. Brattain,et al.  Defective cleavage of membrane bound TGFα leads to enhanced activation of the EGF receptor in malignant cells , 2000, Oncogene.

[475]  R. Black,et al.  Growth Hormone (GH)-induced Dimerization Inhibits Phorbol Ester-stimulated GH Receptor Proteolysis* , 2001, The Journal of Biological Chemistry.

[476]  K. Horiuchi,et al.  ADAM12 and ADAM17 are essential molecules for hypoxia-induced impairment of neural vascular barrier function , 2015, Scientific Reports.

[477]  Qunhua Huang,et al.  Metalloproteinase‐dependent cleavage of neuregulin and autocrine stimulation of vascular endothelial cells , 2010, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[478]  Pål Aukrust,et al.  Cytokines as new treatment targets in chronic heart failure , 2001, Current controlled trials in cardiovascular medicine.

[479]  J. Couchman,et al.  Cellular roles of ADAM12 in health and disease. , 2008, The international journal of biochemistry & cell biology.

[480]  S. Goerdt,et al.  Counter-regulation of the ligand-receptor pair Leda-1/Pianp and Pilrα during the LPS-mediated immune response of murine macrophages. , 2015, Biochemical and biophysical research communications.

[481]  R. Dickson,et al.  Regulation of the activity of matriptase on epithelial cell surfaces by a blood-derived factor. , 2001, European journal of biochemistry.

[482]  R. Leduc,et al.  Ectodomain shedding of furin: kinetics and role of the cysteine‐rich region , 2002, FEBS letters.

[483]  P. Lamy,et al.  Corrigendum to “HER2 shedding and serum HER2 extracellular domain: Biology and clinical utility in breast cancer” [Cancer Treat Rev 2012; 38: 133–142] , 2013 .