Thromb Haemost 2003; 89(04): 622-631
DOI: 10.1055/s-0037-1613568
Review Article
Schattauer GmbH

The ADAMs family of proteins: from basic studies to potential clinical applications

Michael J. Duffy
1   Department of Nuclear Medicine, St Vincent’s University Hospital, Dublin, Ireland
2   Department of Surgery, Conway Institute of Biomolecular Science and Biomedical Research, University College Dublin, Dublin, Ireland
,
David J. Lynn
3   Department of Medicine, University College Dublin, Dublin, Ireland
1   Department of Nuclear Medicine, St Vincent’s University Hospital, Dublin, Ireland
,
Andrew T. Lloyd
4   Department of Genetics, Trinity College Dublin, Dublin, Ireland
1   Department of Nuclear Medicine, St Vincent’s University Hospital, Dublin, Ireland
,
Caroline M. O’Shea
2   Department of Surgery, Conway Institute of Biomolecular Science and Biomedical Research, University College Dublin, Dublin, Ireland
1   Department of Nuclear Medicine, St Vincent’s University Hospital, Dublin, Ireland
› Author Affiliations
Financial support: This work was supported by the Irish Cancer Society and the Irish Department of Agriculture.
Further Information

Publication History

Received 08 November 2002

Accepted after revision 30 January 2003

Publication Date:
07 December 2017 (online)

Summary

The ADAMs are a family of membrane proteins possessing a disintegrin and metalloprotease domain. Currently,34 members are known to exist. Approximately 50% of the ADAMs contain a metalloprotease-like domain and some of these have been shown to possess protease activity. Most of the protein substrates identified to date for ADAMs are either integral membrane or extracellular matrix (ECM) proteins. In addition to hydrolysing proteins, a number of ADAMs bind to integrins. The attachment to integrins occurs via the disintegrin domain. Since the ADAMs can play a role in both proteolysis and adhesion, they have been implicated in a variety of biological processes such as sperm-egg fusion, somatic cell-cell adhesion, ecto-domain shedding, myoblast fusion and development. Altered expression of certain ADAMs has been associated with a number of diseases including asthma, arthritis, Alzheimer’s disease, atherosclerosis and cancer.

Theme paper: Part of this paper was originally presented at the joint meetings of the 16th International Congress of the International Society of Fibrinolysis and Proteolysis (ISFP) and the 17th International Fibrinogen Workshop of the International Fibrinogen Research Society (IFRS) held in Munich, Germany, September, 2002.

 
  • References

  • 1 Stone AL, Kroeger M, Sang QX. Structure-function analysis of the ADAM family of dis-integrin-like and metalloproteinase-containing proteins (review). J Protein Chem 1999; 18 (04) 447-65.
  • 2 Primakoff P, Myles DG. The ADAM gene family: surface proteins with adhesion and protease activity. Trends Genet 2000; 16 (02) 83-7.
  • 3 Stocker W, Grams F, Baumann U. et al. The metzincins—topological and sequential relations between the astacins, adamalysins, serralysins, and matrixins (collagenases) define a superfamily of zinc-peptidases. Protein Sci 1995; 4 (05) 823-40.
  • 4 Black RA, White JM. ADAMs: focus on the protease domain. Curr Opin Cell Biol 1998; 10 (05) 654-9.
  • 5 Killar L, White J, Black R, Peschon J. Adamalysins. A family of metzincins including TNF-alpha converting enzyme (TACE). Ann N Y Acad Sci 1999; 878: 442-52.
  • 6 Jia LG, Shimokawa K, Bjarnason JB, Fox JW. Snake venom metalloproteinases: structure, function and relationship to the ADAMs family of proteins. Toxicon 1996; 34 11-12 1269-76.
  • 7 Katagiri T, Harada Y, Emi M, Nakamura Y. Human metalloprotease/disintegrin-like (MDC) gene: exon-intron organization and alternative splicing. Cytogenet Cell Genet 1995; 68 1-2 39-44.
  • 8 Gilpin BJ, Loechel F, Mattei MG, Engvall E, Albrechtsen R, Wewer UM. A novel, secreted form of human ADAM 12 (meltrin alpha) provokes myogenesis in vivo. J Biol Chem 1998; 273 (01) 157-66.
  • 9 Roghani M, Becherer JD, Moss ML. et al. Metalloprotease-disintegrin MDC 9: intracellular maturation and catalytic activity. J Biol Chem 1999; 274 (06) 3531-40.
  • 10 Gaultier A, Cousin H, Darribere T, Alfandari D. ADAM13 disintegrin and cysteine-rich domains bind to the second heparin-binding domain of fibronectin. J Biol Chem 2002; 277 (26) 23336-44.
  • 11 Nagase H. Activation mechanisms of matrix metalloproteinases. Biol Chem 1997; 378 3-4 151-60.
  • 12 Loechel F, Overgaard MT, Oxvig C, Albrechtsen R, Wewer UM. Regulation of human ADAM 12 protease by the prodomain. Evidence for a functional cysteine switch. J Biol Chem 1999; 274 (19) 13427-33.
  • 13 Anders A, Gilbert S, Garten W, Postina R, Fahrenholz F. Regulation of the alpha-secretase ADAM10 by its prodomain and proprotein convertases. FASEB J 2001; 15 (10) 1837-9.
  • 14 Amour A, Knight CG, English WR. et al. The enzymatic activity of ADAM8 and ADAM9 is not regulated by TIMPs. FEBS Lett 2002; 524 1-3 154-158.
  • 15 Izumi Y, Hirata M, Hasuwa H. et al. A metal-loprotease-disintegrin, MDC9/meltrin-gamma/ ADAM9 and PKCdelta are involved in TPA-induced ectodomain shedding of membrane-anchored heparin-binding EGF-like growth factor. EMBO J 1998; 17 (24) 7260-72.
  • 16 Schwettmann L, Tschesche H. Cloning and expression in Pichia pastoris of metalloprotease domain of ADAM 9 catalytically active against fibronectin. Protein Expr Purif 2001; 21 (01) 65-70.
  • 17 Hotoda N, Koike H, Sasagawa N, Ishiura S. A secreted form of human ADAM9 has an alpha-secretase activity for APP. Biochem Biophys Res Commun 2002; 293 (02) 800-5.
  • 18 Franzke CW, Tasanen K, Schacke H. et al. Transmembrane collagen XVII, an epithelial adhesion protein, is shed from the cell surface by ADAMs. EMBO J 2002; 21 (19) 5026-35.
  • 19 Millichip I M, Dallas DJ, Wu E, Dale S, McKie N. The metallo-disintegrin ADAM10 (MADM) from bovine kidney has type IV collagenase activity in vitro. Biochem Biophys Res Commun 1998; 245 (02) 594-8.
  • 20 Mechtersheimer S, Gutwein P, Agmon-Levin N. et al. Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins. J Cell Biol 2001; 155 (04) 661-73.
  • 21 Lunn CA, Fan X, Dalie B. et al. Purification of ADAM 10 from bovine spleen as a TNFalpha convertase. FEBS Lett 1997; 400 (03) 333-5.
  • 22 Lammich S, Kojro E, Postina R. et al. Constitutive and regulated alpha-secretase cleavage of Alzheimer’s amyloid precursor protein by a disintegrin metalloprotease. Proc Natl Acad Sci U S A 1999; 96 (07) 3922-7.
  • 23 Rosendahl MS, Ko SC, Long DL. et al. Identification and characterization of a pro-tumor necrosis factor-alpha processing enzyme from the ADAM family of zinc metallo-proteases. J Biol Chem 1997; 272 (39) 24588-93.
  • 24 Yan Y, Shirakabe K, Werb Z. The metallopro-tease Kuzbanian (ADAM10) mediates the trans-activation of EGF receptor by G protein-coupled receptors. J Cell Biol 2002; 158 (02) 221-6.
  • 25 Pan D, Rubin GM. Kuzbanian controls proteolytic processing of Notch and mediates lateral inhibition during Drosophila and vertebrate neurogenesis. Cell 1997; 90 (02) 271-80.
  • 26 Qi H, Rand MD, Wu X. et al. Processing of the notch ligand delta by the metalloprotease Kuzbanian. Science 1999; 283 5398 91-4.
  • 27 Asakura M, Kitakaze M, Takashima S. et al. Cardiac hypertrophy is inhibited by antagonism of ADAM12 processing of HB-EGF: metalloproteinase inhibitors as a new therapy. Nat Med 2002; 8 (01) 35-40.
  • 28 Alfandari D, Cousin H, Gaultier A. et al. Xenopus ADAM 13 is a metalloprotease required for cranial neural crest-cell migration. Curr Biol 2001; 11 (12) 918-30.
  • 29 Martin J, Eynstone LV, Davies M, Steadman R. The role of ADAM 15 in glomerular mesangial cell migration. J Biol Chem 2002; 277 (37) 33683-9.
  • 30 Moss ML, Jin SL, Milla ME, Bickett DM, Burkhart W, Carter HL. et al. Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha. Nature 1997; 385 6618 733-6.
  • 31 Black RA, Rauch CT, Kozlosky CJ. et al. A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells. Nature 1997; 385 6618 729-33.
  • 32 Thathiah A, Blobel CP, Carson DD. Tumor necrosis factor-alpha converting enzyme (TACE)/ADAM 17 mediates MUC1 shedding. J Biol Chem 2002; 278 (05) 3386-94.
  • 33 Peschon JJ, Slack JL, Reddy P. et al. An essential role for ectodomain shedding in mammalian development. Science 1998; 282 5392 1281-4.
  • 34 Sunnarborg SW, Hinkle CL, Stevenson M. et al. Tumor necrosis factor-alpha converting enzyme (TACE) regulates epidermal growth factor receptor ligand availability. J Biol Chem 2002; 277 (15) 12838-45.
  • 35 Yamamoto S, Higuchi Y, Yoshiyama K. et al. ADAM family proteins in the immune system. Immunol Today 1999; 20 (06) 278-84.
  • 36 Schlondorff J, Blobel CP. Metalloproteasedisintegrins: modular proteins capable of promoting cell-cell interactions and triggering signals by protein-ectodomain shedding. J Cell Sci 1999; 112 Pt 21 3603-17.
  • 37 Shirakabe K, Wakatsuki S, Kurisaki T, Fujisawa-Sehara A. Roles of Meltrin beta/ ADAM19 in the processing of neuregulin. J Biol Chem 2001; 276 (12) 9352-8.
  • 38 van der Flier A, Sonnenberg A. Function and interactions of integrins. Cell Tissue Res 2001; 305 (03) 285-98.
  • 39 Frenette PS, Wagner DD. Adhesion molecules—Part 1. N Engl J Med 1996; 334 (23) 1526-9.
  • 40 Nath D, Slocombe PM, Stephens PE. et al. Interaction of metargidin (ADAM-15) with alphavbeta3 and alpha5beta1 integrins on different haemopoietic cells. J Cell Sci 1999; 112 Pt 4 579-87.
  • 41 Zhang XP, Kamata T, Yokoyama K, Puzon-McLaughlin W, Takada Y. Specific interaction of the recombinant disintegrin-like domain of MDC- 15 (metargidin, ADAM-15) with inte-grin alphavbeta3. J Biol Chem 1998; 273 (13) 7345-50.
  • 42 Evans JP. Fertilin beta and other ADAMs as integrin ligands: insights into cell adhesion and fertilization. Bioessays 2001; 23 (07) 628-39.
  • 43 Eto K, Huet C, Tarui T, Kupriyanov S. et al. Functional classification of ADAMs based on a conserved motif for binding to integrin alpha 9beta 1: implications for sperm-egg binding and other cell interactions. J Biol Chem 2002; 277 (20) 17804-10.
  • 44 Ham C, Levkau B, Raines EW, Herren B. ADAM15 is an adherens junction molecule whose surface expression can be driven by VE-cadherin. Exp Cell Res 2002; 279 (02) 239-47.
  • 45 Bigler D, Takahashi Y, Chen MS, Almeida EA, Osbourne L, White JM. Sequence-specific interaction between the disintegrin domain of mouse ADAM 2 (fertilin beta) and murine eggs. Role of the alpha(6) integrin subunit. J Biol Chem 2000; 275 (16) 11576-84.
  • 46 Chen H, Sampson NS. Mediation of sperm-egg fusion: evidence that mouse egg alpha6beta1 integrin is the receptor for sperm fertilin beta. Chem Biol 1999; 6 (01) 1-10.
  • 47 Nath D, Slocombe PM, Webster A, Stephens PE, Docherty AJ, Murphy G. Meltrin gamma (ADAM-9) mediates cellular adhesion through alpha(6)beta(1 )integrin, leading to a marked induction of fibroblast cell motility. J Cell Sci 2000; 113 Pt 12 2319-28.
  • 48 Zhou M, Graham R, Russell G, Croucher I P. MDC-9 (ADAM-9/Meltrin gamma) functions as an adhesion molecule by binding the alpha(v)beta(5) integrin. Biochem Biophys Res Commun 2001; 280 (02) 574-80.
  • 49 Eto K, Puzon-McLaughlin W, Sheppard D, Sehara-Fujisawa A, Zhang XP, Takada Y. RGD-independent binding of integrin alpha9beta1 to the ADAM-12 and -15 disinte-grin domains mediates cell-cell interaction. J Biol Chem 2000; 275 (45) 34922-30.
  • 50 Cal S, Freije JM, Lopez JM, Takada Y, Lopez-Otin C. ADAM 23/MDC3, a human disinte-grin that promotes cell adhesion via interaction with the alphavbeta3 integrin through an RGD-independent mechanism. Mol Biol Cell 2000; 11 (04) 1457-69.
  • 51 Bridges LC, Tani PH, Hanson KR, Roberts CM, Judkins MB, Bowditch RD. The lymphocyte metalloprotease MDC-L (ADAM 28) is a ligand for the integrin alpha4beta1. J Biol Chem 2002; 277 (05) 3784-92.
  • 52 Iba K, Albrechtsen R, Gilpin B. et al. The cysteine-rich domain of human ADAM 12 supports cell adhesion through syndecans and triggers signaling events that lead to beta1 integrin-dependent cell spreading. J Cell Biol 2000; 149 (05) 1143-56.
  • 53 Smith KM, Gaultier A, Cousin H, Alfandari D, White JM, DeSimone DW. The cysteine-rich domain regulates ADAM protease function in vivo. J Cell Biol 2002; 159 (05) 893-902.
  • 54 Huovila AP, Almeida EA, White JM. ADAMs and cell fusion. Curr Opin Cell Biol 1996; 8 (05) 692-9.
  • 55 Wolfsberg TG, Primakoff P, Myles DG, White JM. ADAM, a novel family of membrane proteins containing A Disintegrin And Metallo-protease domain: multipotential functions in cell-cell and cell- matrix interactions. J Cell Biol 1995; 131 (02) 275-8.
  • 56 Blobel CP, Wolfsberg TG, Turck CW, Myles DG, Primakoff P, White JM. A potential fusion peptide and an integrin ligand domain in a protein active in sperm-egg fusion. Nature 1992; 356 6366 248-52.
  • 57 Namba K, Nishio M, Mori K. et al. Involvement of ADAM9 in multinucleated giant cell formation of blood monocytes. Cell Immunol 2001; 213 (02) 104-13.
  • 58 Yagami-Hiromasa T, Sato T, Kurisaki T, Kamijo K, Nabeshima Y, Fujisawa-Sehara A. A metalloprotease-disintegrin participating in myoblast fusion. Nature 1995; 377 6550 652-6.
  • 59 Howard L, Nelson KK, Maciewicz RA, Blobel CP. Interaction of the metalloprotease disinte-grins MDC9 and MDC15 with two SH3 domain-containing proteins, endophilin I and SH3PX1. J Biol Chem 1999; 274 (44) 31693-9.
  • 60 Nelson KK, Schlondorff J, Blobel CP. Evidence for an interaction of the metallopro-tease-disintegrin tumour necrosis factor alpha convertase (TACE) with mitotic arrest deficient 2 (MAD2), and of the metalloproteasedisintegrin MDC9 with a novel MAD2-related protein, MAD2beta. Biochem J 1999; 343 Pt 3 673-80.
  • 61 Weskamp G, Kratzschmar J, Reid MS, Blobel CP. MDC9, a widely expressed cellular disintegrin containing cytoplasmic SH3 ligand domains. J Cell Biol 1996; 132 (04) 717-26.
  • 62 Cao Y, Kang Q, Zolkiewska A. Metallopro-tease-disintegrin ADAM 12 interacts with alpha-actinin-1. Biochem J 2001; 357 Pt 2 353-61.
  • 63 Galliano MF, Huet C, Frygelius J, Polgren A, Wewer UM, Engvall E. Binding of ADAM12, a marker of skeletal muscle regeneration, to the muscle-specific actin-binding protein, alpha-actinin-2, is required for myoblast fusion. J Biol Chem 2000; 275 (18) 13933-9.
  • 64 Kang Q, Cao Y, Zolkiewska A. Metallopro-tease-disintegrin ADAM 12 binds to the SH3 domain of Src and activates Src tyrosine kinase in C2C12 cells. Biochem J 2000; 352 Pt 3 883-92.
  • 65 Kang Q, Cao Y, Zolkiewska A. Direct interaction between the cytoplasmic tail of ADAM 12 and the Src homology 3 domain of p85alpha activates phosphatidylinositol 3-kinase in C2C12 cells. J Biol Chem 2001; 276 (27) 24466-72.
  • 66 Thodeti CK, Albrechtsen R, Grauslund M. et al. ADAM12/syndecan-4 signaling promotes beta 1 integrin-dependent cell spreading through PKCalpha and RhoA.. J Biol Chem 2002 In press
  • 67 Poghosyan Z, Robbins SM, Houslay MD, Webster A, Murphy G, Edwards DR. Phosphorylation-dependent interactions between ADAM15 cytoplasmic domain and Src family protein-tyrosine kinases. J Biol Chem 2002; 277 (07) 4999-5007.
  • 68 Zheng Y, Schlondorff J, Blobel CP. Evidence for regulation of the tumor necrosis factor alpha-convertase (TACE) by protein-tyrosine phosphatase PTPH1. J Biol Chem 2002; 277 (45) 42463-70.
  • 69 Thompson JD, Higgins DG, Gibson TJ. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 1994; 22 (22) 4673-80.
  • 70 Kurisaki T, Masuda A, Osumi N, Nabeshima Y, Fujisawa-Sehara A. Spatially- and temporally-restricted expression of meltrin alpha (ADAM12) and beta (ADAM19) in mouse embryo. Mech Dev 1998; 73 (02) 211-5.
  • 71 Herren B, Raines EW, Ross R. Three putative integrin ligands identified in human aortic smooth muscle cells. Ann N Y Acad Sci 1997; 811: 498-505.
  • 72 Van Eerdewegh P, Little RD, Dupuis J. et al. Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness. Nature 2002; 418 6896 426-30.
  • 73 Sagane K, Ohya Y, Hasegawa Y, Tanaka I. Metalloproteinase-like, disintegrin-like, cysteine-rich proteins MDC2 and MDC 3: novel human cellular disintegrins highly expressed in the brain. Biochem J 1998; 334 Pt 1 93-8.
  • 74 Maskos K, Fernandez-Catalan C, Huber R. et al. Crystal structure of the catalytic domain of human tumor necrosis factor-alpha-converting enzyme. Proc Natl Acad Sci U S A 1998; 95 (07) 3408-12.
  • 75 Mizui Y, Yamazaki K, Sagane K, Tanaka I. cDNA cloning of mouse tumor necrosis factor-alpha converting enzyme (TACE) and partial analysis of its promoter. Gene 1999; 233 1-2 67-74.
  • 76 Cerretti DP, Poindexter K, Castner BJ. et al. Characterization of the cDNA and gene for mouse tumour necrosis factor alpha converting enzyme (TACE/ADAM17) and its location to mouse chromosome 12 and human chromosome 2p25. Cytokine 1999; 11 (08) 541-51.
  • 77 Kurohara K, Matsuda Y, Nagabukuro A, Tsuji A, Amagasa T, Fujisawa-Sehara A. Meltrin beta (ADAM19) gene: cloning, mapping, and analysis of the regulatory region. Biochem Biophys Res Commun 2000; 270 (02) 522-7.
  • 78 Azizkhan JC, Jensen DE, Pierce AJ, Wade M. Transcription from TATA-less promoters: dihydrofolate reductase as a model. Crit Rev Eukaryot Gene Expr 1993; 3 (04) 229-54.
  • 79 Dynan W. Promoters for housekeeping genes. Trends Genet 1986; 2: 196-7.
  • 80 Westermarck J, Kahari VM. Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J 1999; 13 (08) 781-92.
  • 81 Dittmer J, Nordheim A. Ets transcription factors and human disease. Biochim Biophys Acta 1998; 1377 (02) F1-11.
  • 82 Higashiyama S, Abraham JA, Miller J, Fiddes JC, Klagsbrun M. A heparin-binding growth factor secreted by macrophage-like cells that is related to EGF. Science 1991; 251 4996 936-9.
  • 83 McDermott MF. TNF and TNFR biology in health and disease. Cell Mol Biol (Noisy-le-grand) 2001; 47 (04) 619-35.
  • 84 Moore RJ, Owens DM, Stamp G. et al. Mice deficient in tumor necrosis factor-alpha are resistant to skin carcinogenesis. Nat Med 1999; 5 (07) 828-31.
  • 85 Li Z, Shimada Y, Uchida S, Maeda M. et al. TGF-alpha as well as VEGF, PD-ECGF and bFGF contribute to angiogenesis of esophageal squamous cell carcinoma. Int J Oncol 2000; 17 (03) 453-60.
  • 86 Duffy MJ. The biochemistry of metastasis. Adv Clin Chem 1996; 32: 135-66.
  • 87 Duffy MJ. The role of proteolytic enzymes in cancer invasion and metastasis. Clin Exp Metastasis 1992; 10 (03) 145-55.
  • 88 Kadmon G, Altevogt P. The cell adhesion molecule L 1: species- and cell-type-dependent multiple binding mechanisms. Differentiation 1997; 61 (03) 143-50.
  • 89 Wu E, Croucher I P, McKie N. Expression of members of the novel membrane linked metal-loproteinase family ADAM in cells derived from a range of haematological malignancies. Biochem Biophys Res Commun 1997; 235 (02) 437-42.
  • 90 O’ Shea C, McKie N, Buggy Y. et al. Expression of ADAM-9 mRNA and protein in human breast cancer. Int J Cancer. 2003 In press
  • 91 O’ Shea C, Gray J, McKie N. et al. Expression of ADAM-10 protein in human breast cancer. Tumour Biol 2000; 21 (01) 141.
  • 92 Iba K, Albrechtsen R, Gilpin BJ, Loechel F, Wewer UM. Cysteine-rich domain of human ADAM 12 (meltrin alpha) supports tumor cell adhesion. Am J Pathol 1999; 154 (05) 1489-501.
  • 93 Emi M, Katagiri T, Harada Y. et al. A novel metalloprotease/disintegrin-like gene at 17q21.3 is somatically rearranged in two primary breast cancers. Nat Genet 1993; 5 (02) 151-7.
  • 94 O’ Shea C, Duggan C, Buggy Y. et al. Expression of ADAM-11 splice variants in breast cancer. British Journal of Cancer 2002; 86 (01) S87.
  • 95 Tang BL. ADAMTS: a novel family of extracellular matrix proteases. Int J Biochem Cell Biol 2001; 33 (01) 33-44.
  • 96 McKie N, Edwards T, Dallas DJ. et al. Expression of members of a novel membrane linked metalloproteinase family (ADAM) in human articular chondrocytes. Biochem Biophys Res Commun 1997; 230 (02) 335-9.
  • 97 Chubinskaya S, Mikhail R, Deutsch A, Tindal MH. ADAM-10 protein is present in human articular cartilage primarily in the membrane-bound form and is upregulated in osteoarthritis and in response to IL-1alpha in bovine nasal cartilage. J Histochem Cytochem 2001; 49 (09) 1165-76.
  • 98 Bohm BB, Aigner T, Gehrsitz A, Blobel CP, Kalden JR, Burkhardt H. Up-regulation of MDC15 (metargidin) messenger RNA in human osteoarthritic cartilage. Arthritis Rheum 1999; 42 (09) 1946-50.
  • 99 Bohm BB, Aigner T, Blobel CP, Kalden JR, Burkhardt H. Highly enhanced expression of the disintegrin metalloproteinase MDC15 (metargidin) in rheumatoid synovial tissue. Arthritis Rheum 2001; 44 (09) 2046-54.
  • 100 Abe T, Takeuchi T. Rheumatoid arthritis and tumor necrosis factor alpha. Autoimmunity 2001; 34 (04) 291-303.
  • 101 Shanahan JC, St Clair W. Tumor necrosis factor-alpha blockade: a novel therapy for rheumatic disease. Clin Immunol 2002; 103 3 Pt 1 231-42.
  • 102 Herren B. ADAM-mediated shedding and adhesion: a vascular perspective. News Physiol Sci 2002; 17: 73-6.
  • 103 Herren B, Raines EW, Ross R. Expression of a disintegrin-like protein in cultured human vascular cells and in vivo. FASEB J 1997; 11 (02) 173-80.
  • 104 Shapiro SD, Owen CA. ADAM-33 surfaces as an asthma gene. N Engl J Med 2002; 347: 936-8.
  • 105 Shoji M, Golde TE, Ghiso J, Cheung TT, Estus S, Shaffer LM. et al. Production of the Alzheimer amyloid beta protein by normal proteolytic processing. Science 1992; 258 5079 126-9.
  • 106 Skovronsky DM, Moore DB, Milla ME, Doms RW, Lee VM. Protein kinase C-dependent alpha-secretase competes with beta-secretase for cleavage of amyloid-beta precursor protein in the trans-golgi network. J Biol Chem 2000; 275 (04) 2568-75.
  • 107 Hartmann D, de Strooper B, Serneels L. et al. The disintegrin/metalloprotease ADAM 10 is essential for Notch signalling but not for alpha-secretase activity in fibroblasts. Hum Mol Genet 2002; 11 (21) 2615-24.