Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 13 November 1998:
Vol. 282. no. 5392, pp. 1279 - 1280
DOI: 10.1126/science.282.5392.1279
Prev | Table of Contents | Next

Perspectives

Also see the archival list of Science's Compass: Enhanced Perspectives

CELL BIOLOGY:
Enhanced: A Cellular Striptease Act

Zena Werb and Yibing Yan

Proteins on the cell surface can be cleaved by proteolytic enzymes. In the Perspective, Werb and Yan outline the many purposes of these cleavage events-to provide ligand for binding to receptors (as shown in the report by Peschon et al. on p. 1281), to eliminate ligand on receptors and to increase or decrease cell-cell interactions. Such proteolysis can be regulated and is turning out to be widely used by the cell.

The authors are at the Department of Anatomy, University of California, San Francisco, CA 94143-0452, USA. E mail: zena@itsa.ucsf.edu; yan@cgl.ucsf.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The Identification of a Calmodulin-Binding Domain within the Cytoplasmic Tail of Angiotensin-Converting Enzyme-2.
Z. W. Lai, R. A. Lew, M. A. Yarski, F.-T. Mu, R. K. Andrews, and A. I. Smith (2009)
Endocrinology 150, 2376-2381
   Abstract »    Full Text »    PDF »
Tumor necrosis factor inhibits ligand-stimulated EGF receptor activation through a TNF receptor 1-dependent mechanism.
S. J. McElroy, M. R. Frey, F. Yan, K. L. Edelblum, J. A. Goettel, S. John, and D. B. Polk (2008)
Am J Physiol Gastrointest Liver Physiol 295, G285-G293
   Abstract »    Full Text »    PDF »
Shedding of the Urinary Biomarker Kidney Injury Molecule-1 (KIM-1) Is Regulated by MAP Kinases and Juxtamembrane Region.
Z. Zhang, B. D. Humphreys, and J. V. Bonventre (2007)
J. Am. Soc. Nephrol. 18, 2704-2714
   Abstract »    Full Text »    PDF »
Shedding of Collagen XXIII Is Mediated by Furin and Depends on the Plasma Membrane Microenvironment.
G. Veit, E. P. Zimina, C.-W. Franzke, S. Kutsch, U. Siebolds, M. K. Gordon, L. Bruckner-Tuderman, and M. Koch (2007)
J. Biol. Chem. 282, 27424-27435
   Abstract »    Full Text »    PDF »
Regulation of Oxidant-Induced Intestinal Permeability by Metalloprotease-Dependent Epidermal Growth Factor Receptor Signaling.
C. B. Forsyth, A. Banan, A. Farhadi, J. Z. Fields, Y. Tang, M. Shaikh, L. J. Zhang, P. A. Engen, and A. Keshavarzian (2007)
J. Pharmacol. Exp. Ther. 321, 84-97
   Abstract »    Full Text »    PDF »
Modulation of the Cellular Cholesterol Level Affects Shedding of the Type XIII Collagen Ectodomain.
T. Vaisanen, M.-R. Vaisanen, and T. Pihlajaniemi (2006)
J. Biol. Chem. 281, 33352-33362
   Abstract »    Full Text »    PDF »
Ectodomain Shedding of Preadipocyte Factor 1 (Pref-1) by Tumor Necrosis Factor Alpha Converting Enzyme (TACE) and Inhibition of Adipocyte Differentiation..
Y. Wang and H. S. Sul (2006)
Mol. Cell. Biol. 26, 5421-5435
   Abstract »    Full Text »    PDF »
Emerging roles for ectodomain shedding in the regulation of inflammatory responses.
K. J. Garton, P. J. Gough, and E. W. Raines (2006)
J. Leukoc. Biol. 79, 1105-1116
   Abstract »    Full Text »    PDF »
Tumor Necrosis Factor-{alpha}-converting Enzyme (TACE/ADAM-17) Mediates the Ectodomain Cleavage of Intercellular Adhesion Molecule-1 (ICAM-1).
N. L. Tsakadze, S. D. Sithu, U. Sen, W. R. English, G. Murphy, and S. E. D'Souza (2006)
J. Biol. Chem. 281, 3157-3164
   Abstract »    Full Text »    PDF »
Lung-marginated Monocytes Modulate Pulmonary Microvascular Injury during Early Endotoxemia.
K. P. O'Dea, A. J. Young, H. Yamamoto, J. L. Robotham, F. M. Brennan, and M. Takata (2005)
Am. J. Respir. Crit. Care Med. 172, 1119-1127
   Abstract »    Full Text »    PDF »
Calmodulin Binds to the Cytoplasmic Domain of Angiotensin-converting Enzyme and Regulates Its Phosphorylation and Cleavage Secretion.
S. Chattopadhyay, K. R. Santhamma, S. Sengupta, B. McCue, M. Kinter, G. C. Sen, and I. Sen (2005)
J. Biol. Chem. 280, 33847-33855
   Abstract »    Full Text »    PDF »
Role of Meltrin {alpha} (ADAM12) in Obesity Induced by High- Fat Diet.
M. Masaki, T. Kurisaki, K. Shirakawa, and A. Sehara-Fujisawa (2005)
Endocrinology 146, 1752-1763
   Abstract »    Full Text »    PDF »
Regulation of platelet membrane levels of glycoprotein VI by a platelet-derived metalloproteinase.
E. E. Gardiner, J. F. Arthur, M. L. Kahn, M. C. Berndt, and R. K. Andrews (2004)
Blood 104, 3611-3617
   Abstract »    Full Text »    PDF »
Role of Tyrosine Phosphorylation in the Regulation of Cleavage Secretion of Angiotensin-converting Enzyme.
K. R. Santhamma, R. Sadhukhan, M. Kinter, S. Chattopadhyay, B. McCue, and I. Sen (2004)
J. Biol. Chem. 279, 40227-40236
   Abstract »    Full Text »    PDF »
Inhibition of the Tumor Necrosis Factor-{alpha}-converting Enzyme by Its Pro Domain.
P. E. Gonzales, A. Solomon, A. B. Miller, M. A. Leesnitzer, I. Sagi, and M. E. Milla (2004)
J. Biol. Chem. 279, 31638-31645
   Abstract »    Full Text »    PDF »
Selective Roles for Tumor Necrosis Factor {alpha}-converting Enzyme/ADAM17 in the Shedding of the Epidermal Growth Factor Receptor Ligand Family: THE JUXTAMEMBRANE STALK DETERMINES CLEAVAGE EFFICIENCY.
C. L. Hinkle, S. W. Sunnarborg, D. Loiselle, C. E. Parker, M. Stevenson, W. E. Russell, and D. C. Lee (2004)
J. Biol. Chem. 279, 24179-24188
   Abstract »    Full Text »    PDF »
Heparin-Binding Epidermal Growth Factor Cleavage Mediates Zinc-Induced Epidermal Growth Factor Receptor Phosphorylation.
W. Wu, J. M. Samet, R. Silbajoris, L. A. Dailey, D. Sheppard, P. A. Bromberg, and L. M. Graves (2004)
Am. J. Respir. Cell Mol. Biol. 30, 540-547
   Abstract »    Full Text »    PDF »
Molecular Modifications of MC31/CE9, a Sperm Surface Molecule, During Sperm Capacitation and the Acrosome Reaction in the Rat: Is MC31/CE9 Required for Fertilization?.
D. K. Saxena and K. Toshimori (2004)
Biol Reprod 70, 993-1000
   Abstract »    Full Text »    PDF »
Membrane-associated HB-EGF modulates HGF-induced cellular responses in MDCK cells.
A. B. Singh, T. Tsukada, R. Zent, and R. C. Harris (2004)
J. Cell Sci. 117, 1365-1379
   Abstract »    Full Text »    PDF »
The ectodomain shedding of angiotensin-converting enzyme is independent of its localisation in lipid rafts.
E. T. Parkin, F. Tan, R. A. Skidgel, A. J. Turner, and N. M. Hooper (2003)
J. Cell Sci. 116, 3079-3087
   Abstract »    Full Text »    PDF »
Impaired Trafficking and Activation of Tumor Necrosis Factor-{alpha}-converting Enzyme in Cell Mutants Defective in Protein Ectodomain Shedding.
A. Borroto, S. Ruiz-Paz, T. V. de la Torre, M. Borrell-Pages, A. Merlos-Suarez, A. Pandiella, C. P. Blobel, J. Baselga, and J. Arribas (2003)
J. Biol. Chem. 278, 25933-25939
   Abstract »    Full Text »    PDF »
Integrin shedding as a mechanism of cellular adaptation during cardiac growth.
E. C. Goldsmith, W. Carver, A. McFadden, J. G. Goldsmith, R. L. Price, M. Sussman, B. H. Lorell, G. Cooper, and T. K. Borg (2003)
Am J Physiol Heart Circ Physiol 284, H2227-H2234
   Abstract »    Full Text »    PDF »
Characterization of Growth Factor-induced Serine Phosphorylation of Tumor Necrosis Factor-alpha Converting Enzyme and of an Alternatively Translated Polypeptide.
H. Fan, C. W. Turck, and R. Derynck (2003)
J. Biol. Chem. 278, 18617-18627
   Abstract »    Full Text »    PDF »
Notch-induced Proteolysis and Nuclear Localization of the Delta Ligand.
C. E. Bland, P. Kimberly, and M. D. Rand (2003)
J. Biol. Chem. 278, 13607-13610
   Abstract »    Full Text »    PDF »
Tumor Necrosis Factor-alpha Converting Enzyme/ADAM 17 Mediates MUC1 Shedding.
A. Thathiah, C. P. Blobel, and D. D. Carson (2003)
J. Biol. Chem. 278, 3386-3394
   Abstract »    Full Text »    PDF »
Antibody-mediated stripping of CD4 from lymphocyte cell surface in patients with rheumatoid arthritis.
T. W. Hepburn, M. C. Totoritis, and C. B. Davis (2003)
Rheumatology 42, 54-61
   Abstract »    Full Text »    PDF »
TACE mRNA expression in peripheral mononuclear cells precedes new lesions on MRI in multiple sclerosis.
T Seifert, B C Kieseier, S Ropele, S Strasser-Fuchs, F Quehenberger, F Fazekas, and H-P Hartung (2002)
Multiple Sclerosis 8, 447-451
   Abstract »    PDF »
Decreased Expression of Membrane IL-5 Receptor {alpha} on Human Eosinophils: II. IL-5 Down-Modulates Its Receptor Via a Proteinase-Mediated Process.
L. Y. Liu, J. B. Sedgwick, M. E. Bates, R. F. Vrtis, J. E. Gern, H. Kita, N. N. Jarjour, W. W. Busse, and E. A. B. Kelly (2002)
J. Immunol. 169, 6459-6466
   Abstract »    Full Text »    PDF »
ADAM12 Alleviates the Skeletal Muscle Pathology in mdx Dystrophic Mice.
P. Kronqvist, N. Kawaguchi, R. Albrechtsen, X. Xu, H. D. Schroder, B. Moghadaszadeh, F. C. Nielsen, C. Frohlich, E. Engvall, and U. M. Wewer (2002)
Am. J. Pathol. 161, 1535-1540
   Abstract »    Full Text »    PDF »
Shedding of Kidney Injury Molecule-1, a Putative Adhesion Protein Involved in Renal Regeneration.
V. Bailly, Z. Zhang, W. Meier, R. Cate, M. Sanicola, and J. V. Bonventre (2002)
J. Biol. Chem. 277, 39739-39748
   Abstract »    Full Text »    PDF »
The metalloprotease Kuzbanian (ADAM10) mediates the transactivation of EGF receptor by G protein-coupled receptors.
Y. Yan, K. Shirakabe, and Z. Werb (2002)
J. Cell Biol. 158, 221-226
   Abstract »    Full Text »    PDF »
A Unique Substrate Binding Mode Discriminates Membrane Type-1 Matrix Metalloproteinase from Other Matrix Metalloproteinases.
S. J. Kridel, H. Sawai, B. I. Ratnikov, E. I. Chen, W. Li, A. Godzik, A. Y. Strongin, and J. W. Smith (2002)
J. Biol. Chem. 277, 23788-23793
   Abstract »    Full Text »    PDF »
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.
K. Eto, C. Huet, T. Tarui, S. Kupriyanov, H.-Z. Liu, W. Puzon-McLaughlin, X.-P. Zhang, D. Sheppard, E. Engvall, and Y. Takada (2002)
J. Biol. Chem. 277, 17804-17810
   Abstract »    Full Text »    PDF »
Identification of a Soluble Form Phospholipase A2 Receptor as a Circulating Endogenous Inhibitor for Secretory Phospholipase A2.
K.-i. Higashino, Y. Yokota, T. Ono, S. Kamitani, H. Arita, and K. Hanasaki (2002)
J. Biol. Chem. 277, 13583-13588
   Abstract »    Full Text »    PDF »
Tumor Necrosis Factor-alpha Converting Enzyme (TACE) Regulates Epidermal Growth Factor Receptor Ligand Availability.
S. W. Sunnarborg, C. L. Hinkle, M. Stevenson, W. E. Russell, C. S. Raska, J. J. Peschon, B. J. Castner, M. J. Gerhart, R. J. Paxton, R. A. Black, et al. (2002)
J. Biol. Chem. 277, 12838-12845
   Abstract »    Full Text »    PDF »
L-Selectin Shedding Is Independent of Its Subsurface Structures and Topographic Distribution.
B. P. Fors, K. Goodarzi, and U. H. von Andrian (2001)
J. Immunol. 167, 3642-3651
   Abstract »    Full Text »    PDF »
Reduced Blood Vessel Formation and Tumor Growth in {{alpha}}5-Integrin-negative Teratocarcinomas and Embryoid Bodies.
D. Taverna and R. O. Hynes (2001)
Cancer Res. 61, 5255-5261
   Abstract »    Full Text »    PDF »
Antibody-Induced Shedding of CD44 from Adherent Cells Is Linked to the Assembly of the Cytoskeleton.
M. Shi, K. Dennis, J. J. Peschon, R. Chandrasekaran, and K. Mikecz (2001)
J. Immunol. 167, 123-131
   Abstract »    Full Text »    PDF »
Mutations within a furin consensus sequence block proteolytic release of ectodysplasin-A and cause X-linked hypohidrotic ectodermal dysplasia.
Y. Chen, S. S. Molloy, L. Thomas, J. Gambee, H. P. Bachinger, B. Ferguson, J. Zonana, G. Thomas, and N. P. Morris (2001)
PNAS 98, 7218-7223
   Abstract »    Full Text »    PDF »
TNF-{{alpha}}-Converting Enzyme Cleaves the Macrophage Colony-Stimulating Factor Receptor in Macrophages Undergoing Activation.
E. Rovida, A. Paccagnini, M. Del Rosso, J. Peschon, and P. Dello Sbarba (2001)
J. Immunol. 166, 1583-1589
   Abstract »    Full Text »    PDF »
Shedding of c-Met is regulated by crosstalk between a G-protein coupled receptor and the EGF receptor and is mediated by a TIMP-3 sensitive metalloproteinase.
D Nath, N. Williamson, R Jarvis, and G Murphy (2001)
J. Cell Sci. 114, 1213-1220
   Abstract »    PDF »
Release of an invasion promoter E-cadherin fragment by matrilysin and stromelysin-1.
V Noe, B Fingleton, K Jacobs, H. Crawford, S Vermeulen, W Steelant, E Bruyneel, L. Matrisian, and M Mareel (2001)
J. Cell Sci. 114, 111-118
   Abstract »    PDF »
Down-regulation of L-selectin expression in neutrophils by nonsteroidal anti-inflammatory drugs: role of intracellular ATP concentration.
M. V. Gomez-Gaviro, C. Dominguez-Jimenez, J. M. Carretero, P. Sabando, I. Gonzalez-Alvaro, F. Sanchez-Madrid, and F. Diaz-Gonzalez (2000)
Blood 96, 3592-3600
   Abstract »    Full Text »    PDF »
Regulated Cleavage of a Contact-Mediated Axon Repellent.
M. Hattori, M. Osterfield, and J. G. Flanagan (2000)
Science 289, 1360-1365
   Abstract »    Full Text »
TNF-Induced Shedding of TNF Receptors in Human Polymorphonuclear Leukocytes: Role of the 55-kDa TNF Receptor and Involvement of a Membrane-Bound and Non-Matrix Metalloproteinase.
P. Dri, C. Gasparini, R. Menegazzi, R. Cramer, L. Alberi, G. Presani, S. Garbisa, and P. Patriarca (2000)
J. Immunol. 165, 2165-2172
   Abstract »    Full Text »    PDF »
Left Ventricular Hypertrophy in Ascending Aortic Stenosis Mice : Anoikis and the Progression to Early Failure.
B. Ding, R. L. Price, E. C. Goldsmith, T. K. Borg, X. Yan, P. S. Douglas, E. O. Weinberg, J. Bartunek, T. Thielen, V. V. Didenko, et al. (2000)
Circulation 101, 2854-2862
   Abstract »    Full Text »    PDF »
Nitric Oxide Enhances Expression and Shedding of Tumor Necrosis Factor Receptor I (p55) in Endothelial Cells.
M. Okuyama, S. Yamaguchi, M. Yamaoka, J. Nitobe, S. Fujii, T. Yoshimura, and H. Tomoike (2000)
Arterioscler Thromb Vasc Biol 20, 1506-1511
   Abstract »    Full Text »    PDF »
Stimulation-induced Down-regulation of Tumor Necrosis Factor-alpha Converting Enzyme.
J. R. Doedens and R. A. Black (2000)
J. Biol. Chem. 275, 14598-14607
   Abstract »    Full Text »    PDF »
Shedding of Syndecan-1 and -4 Ectodomains Is Regulated by Multiple Signaling Pathways and Mediated by a Timp-3-Sensitive Metalloproteinase.
M. L. Fitzgerald, Z. Wang, P. W. Park, G. Murphy, and M. Bernfield (2000)
J. Cell Biol. 148, 811-824
   Abstract »    Full Text »    PDF »
Proteolytic processing and cell biological functions of the amyloid precursor protein.
B De Strooper and W Annaert (2000)
J. Cell Sci. 113, 1857-1870
   Abstract »    PDF »
The Shedding of Membrane-anchored Heparin-binding Epidermal-like Growth Factor Is Regulated by the Raf/Mitogen-activated Protein Kinase Cascade and by Cell Adhesion and Spreading.
Z.'e. Gechtman, J. L. Alonso, G. Raab, D. E. Ingber, and M. Klagsbrun (1999)
J. Biol. Chem. 274, 28828-28835
   Abstract »    Full Text »    PDF »
Regulated CD44 Cleavage under the Control of Protein Kinase C, Calcium Influx, and the Rho Family of Small G Proteins.
I. Okamoto, Y. Kawano, M. Matsumoto, M. Suga, K. Kaibuchi, M. Ando, and H. Saya (1999)
J. Biol. Chem. 274, 25525-25534
   Abstract »    Full Text »    PDF »
RGD-independent Binding of Integrin alpha 9beta 1 to the ADAM-12 and -15 Disintegrin Domains Mediates Cell-Cell Interaction.
K. Eto, W. Puzon-McLaughlin, D. Sheppard, A. Sehara-Fujisawa, X.-P. Zhang, and Y. Takada (2000)
J. Biol. Chem. 275, 34922-34930
   Abstract »    Full Text »    PDF »
Hepatocyte Growth Factor Activator Inhibitor Type 1 Is a Specific Cell Surface Binding Protein of Hepatocyte Growth Factor Activator (HGFA) and Regulates HGFA Activity in the Pericellular Microenvironment.
H. Kataoka, T. Shimomura, T. Kawaguchi, R. Hamasuna, H. Itoh, N. Kitamura, K. Miyazawa, and M. Koono (2000)
J. Biol. Chem. 275, 40453-40462
   Abstract »    Full Text »    PDF »
A Dual Signaling Cascade That Regulates the Ectodomain Shedding of Heparin-binding Epidermal Growth Factor-like Growth Factor.
T. Umata, M. Hirata, T. Takahashi, F. Ryu, S. Shida, Y. Takahashi, M. Tsuneoka, Y. Miura, M. Masuda, Y. Horiguchi, et al. (2001)
J. Biol. Chem. 276, 30475-30482
   Abstract »    Full Text »    PDF »
Regulation of Membrane Metalloproteolytic Cleavage of L-selectin (CD62L) by the Epidermal Growth Factor Domain.
L.-c. Zhao, M. Shey, M. Farnsworth, and M. O. Dailey (2001)
J. Biol. Chem. 276, 30631-30640
   Abstract »    Full Text »    PDF »
Tumor Necrosis Factor-alpha -converting Enzyme (ADAM17) Mediates the Cleavage and Shedding of Fractalkine (CX3CL1).
K. J. Garton, P. J. Gough, C. P. Blobel, G. Murphy, D. R. Greaves, P. J. Dempsey, and E. W. Raines (2001)
J. Biol. Chem. 276, 37993-38001
   Abstract »    Full Text »    PDF »
Damage-induced neuronal endopeptidase (DINE) is a unique metallopeptidase expressed in response to neuronal damage and activates superoxide scavengers.
S. Kiryu-Seo, M. Sasaki, H. Yokohama, S. Nakagomi, T. Hirayama, S. Aoki, K. Wada, and H. Kiyama (2000)
PNAS 97, 4345-4350
   Abstract »    Full Text »    PDF »
Autocrine loops with positive feedback enable context-dependent cell signaling.
S. Y. Shvartsman, M. P. Hagan, A. Yacoub, P. Dent, H. S. Wiley, and D. A. Lauffenburger (2002)
Am J Physiol Cell Physiol 282, C545-C559
   Abstract »    Full Text »    PDF »
Altered Expression of ADAMs (A Disintegrin And Metalloproteinase) in Fibrillating Human Atria.
M. Arndt, U. Lendeckel, C. Rocken, K. Nepple, C. Wolke, A. Spiess, C. Huth, S. Ansorge, H. U. Klein, and A. Goette (2002)
Circulation 105, 720-725
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)