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Science 13 November 1998:
Vol. 282. no. 5392, pp. 1281 - 1284
DOI: 10.1126/science.282.5392.1281
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Research Articles

An Essential Role for Ectodomain Shedding in Mammalian Development

Jacques J. Peschon, * Jennifer L. Slack, Pranitha Reddy, Kim L. Stocking, Susan W. Sunnarborg, David C. Lee, William E. Russell, Beverly J. Castner, Richard S. Johnson, Jeffrey N. Fitzner, Rogely W. Boyce, Nicole Nelson, Carl J. Kozlosky, Martin F. Wolfson, Charles T. Rauch, Douglas Pat Cerretti, Raymond J. Paxton, Carl J. March, Roy A. Black

The ectodomains of numerous proteins are released from cells by proteolysis to yield soluble intercellular regulators. The responsible protease, tumor necrosis factor-alpha converting enzyme (TACE), has been identified only in the case when tumor necrosis factor-alpha (TNFalpha ) is released. Analyses of cells lacking this metalloproteinase-disintegrin revealed an expanded role for TACE in the processing of other cell surface proteins, including a TNF receptor, the L-selectin adhesion molecule, and transforming growth factor-alpha (TGFalpha ). The phenotype of mice lacking TACE suggests an essential role for soluble TGFalpha in normal development and emphasizes the importance of protein ectodomain shedding in vivo.

J. J. Peschon, J. L. Slack, P. Reddy, K. L. Stocking, B. J. Castner, R. S. Johnson, J. N. Fitzner, N. Nelson, C. J. Kozlosky, M. F. Wolfson, C. T. Rauch, D. P. Cerretti, R. J. Paxton, C. J. March, and R. A. Black are with Immunex Corporation, 51 University Street, Seattle, WA 98101, USA. S. W. Sunnarborg and D. C. Lee are in the Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599-7260, USA. W. E. Russell is in the Departments of Pediatrics and Cell Biology, Vanderbilt University, Nashville, TN 37232, USA. R. W. Boyce is with Pathology Associates International, Frederick, MD 21701, USA.
*   To whom correspondence should be addressed. E-mail: peschon{at}immunex.com

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   Abstract »    Full Text »    PDF »
ADAMs as mediators of EGF receptor transactivation by G protein-coupled receptors.
H. Ohtsu, P. J. Dempsey, and S. Eguchi (2006)
Am J Physiol Cell Physiol 291, C1-C10
   Abstract »    Full Text »    PDF »
CD21 and CD62L shedding are both inducible via P2X7Rs.
S. Sengstake, E.-M. Boneberg, and H. Illges (2006)
Int. Immunol. 18, 1171-1178
   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 »
Schwann cell-derived factor-induced modulation of the NgR/p75NTR/EGFR axis disinhibits axon growth through CNS myelin in vivo and in vitro.
Z. Ahmed, E. L. Suggate, E. R. Brown, R. G. Dent, S. J. Armstrong, L. B. Barrett, M. Berry, and A. Logan (2006)
Brain 129, 1517-1533
   Abstract »    Full Text »    PDF »
Regulation of early lung morphogenesis: questions, facts and controversies.
W. V. Cardoso and J. Lu (2006)
Development 133, 1611-1624
   Abstract »    Full Text »    PDF »
Role of the Epidermal Growth Factor Network in Ovarian Follicles.
M. Conti, M. Hsieh, J.-Y. Park, and Y.-Q. Su (2006)
Mol. Endocrinol. 20, 715-723
   Abstract »    Full Text »    PDF »
A Disintegrin and Metalloproteinase 33 Protein in Patients with Asthma: Relevance to Airflow Limitation.
J.-Y. Lee, S.-W. Park, H. K. Chang, H. Y. Kim, T. Rhim, J.-H. Lee, A.-S. Jang, E.-S. Koh, and C.-S. Park (2006)
Am. J. Respir. Crit. Care Med. 173, 729-735
   Abstract »    Full Text »    PDF »
Chemokine CXCL16, a scavenger receptor, induces proliferation and invasion of first-trimester human trophoblast cells in an autocrine manner.
Y. Huang, X.-Y. Zhu, M.-R. Du, X. Wu, M.-Y. Wang, and D.-J. Li (2006)
Hum. Reprod. 21, 1083-1091
   Abstract »    Full Text »    PDF »
Minireview: The Neuroendocrine Regulation of Puberty: Is the Time Ripe for a Systems Biology Approach?.
S. R. Ojeda, A. Lomniczi, C. Mastronardi, S. Heger, C. Roth, A.-S. Parent, V. Matagne, and A. E. Mungenast (2006)
Endocrinology 147, 1166-1174
   Abstract »    Full Text »    PDF »
Integrins, membrane-type matrix metalloproteinases and ADAMs: Potential implications for cardiac remodeling.
A. M. Manso, L. Elsherif, S.-M. Kang, and R. S. Ross (2006)
Cardiovasc Res 69, 574-584
   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 »
Contribution of TNF-{alpha} Converting Enzyme and Proteinase-3 to TNF-{alpha} Processing in Human Alveolar Macrophages.
L. Armstrong, S. I. H. Godinho, K. M. Uppington, H. A. Whittington, and A. B. Millar (2006)
Am. J. Respir. Cell Mol. Biol. 34, 219-225
   Abstract »    Full Text »    PDF »
Cutting Edge: Tissue Inhibitor of Metalloproteinase 3 Regulates TNF-Dependent Systemic Inflammation.
D. S. Smookler, F. F. Mohammed, Z. Kassiri, G. S. Duncan, T. W. Mak, and R. Khokha (2006)
J. Immunol. 176, 721-725
   Abstract »    Full Text »    PDF »
Hypothalamic Tumor Necrosis Factor-{alpha} Converting Enzyme Mediates Excitatory Amino Acid-Dependent Neuron-to-Glia Signaling in the Neuroendocrine Brain.
A. Lomniczi, A. Cornea, M. E. Costa, and S. R. Ojeda (2006)
J. Neurosci. 26, 51-62
   Abstract »    Full Text »    PDF »
Aspirin Induces Platelet Receptor Shedding via ADAM17 (TACE).
B. Aktas, M. Pozgajova, W. Bergmeier, S. Sunnarborg, S. Offermanns, D. Lee, D. D. Wagner, and B. Nieswandt (2005)
J. Biol. Chem. 280, 39716-39722
   Abstract »    Full Text »    PDF »
Recycling of Cell Surface Pro-transforming Growth Factor-{alpha} Regulates Epidermal Growth Factor Receptor Activation.
S. Martinez-Arca, J. J. Bech-Serra, M. Hurtado-Kuttner, A. Borroto, and J. Arribas (2005)
J. Biol. Chem. 280, 36970-36977
   Abstract »    Full Text »    PDF »
Soluble Axl Is Generated by ADAM10-Dependent Cleavage and Associates with Gas6 in Mouse Serum.
V. Budagian, E. Bulanova, Z. Orinska, E. Duitman, K. Brandt, A. Ludwig, D. Hartmann, G. Lemke, P. Saftig, and S. Bulfone-Paus (2005)
Mol. Cell. Biol. 25, 9324-9339
   Abstract »    Full Text »    PDF »
L1 Is Sequentially Processed by Two Differently Activated Metalloproteases and Presenilin/{gamma}-Secretase and Regulates Neural Cell Adhesion, Cell Migration, and Neurite Outgrowth.
T. Maretzky, M. Schulte, A. Ludwig, S. Rose-John, C. Blobel, D. Hartmann, P. Altevogt, P. Saftig, and K. Reiss (2005)
Mol. Cell. Biol. 25, 9040-9053
   Abstract »    Full Text »    PDF »
Critical Function for ADAM9 in Mouse Prostate Cancer.
L. Peduto, V. E. Reuter, D. R. Shaffer, H. I. Scher, and C. P. Blobel (2005)
Cancer Res. 65, 9312-9319
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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 »
Regulating the dynamics of EGF receptor signaling in space and time.
B.-Z. Shilo (2005)
Development 132, 4017-4027
   Abstract »    Full Text »    PDF »
Neutrophil Elastase Induces MUC5AC Mucin Production in Human Airway Epithelial Cells via a Cascade Involving Protein Kinase C, Reactive Oxygen Species, and TNF-{alpha}-Converting Enzyme.
M. X. G. Shao and J. A. Nadel (2005)
J. Immunol. 175, 4009-4016
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Mammary ductal morphogenesis requires paracrine activation of stromal EGFR via ADAM17-dependent shedding of epithelial amphiregulin.
M. D. Sternlicht, S. W. Sunnarborg, H. Kouros-Mehr, Y. Yu, D. C. Lee, and Z. Werb (2005)
Development 132, 3923-3933
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Tumor Necrosis Factor-{alpha} Convertase (ADAM17) Mediates Regulated Ectodomain Shedding of the Severe-acute Respiratory Syndrome-Coronavirus (SARS-CoV) Receptor, Angiotensin-converting Enzyme-2 (ACE2).
D. W. Lambert, M. Yarski, F. J. Warner, P. Thornhill, E. T. Parkin, A. I. Smith, N. M. Hooper, and A. J. Turner (2005)
J. Biol. Chem. 280, 30113-30119
   Abstract »    Full Text »    PDF »
Up regulated expression of tumour necrosis factor {alpha} converting enzyme in peripheral monocytes of patients with early systemic sclerosis.
T Bohgaki, Y Amasaki, N Nishimura, M Bohgaki, Y Yamashita, M Nishio, K-i Sawada, S Jodo, T Atsumi, and T Koike (2005)
Ann Rheum Dis 64, 1165-1173
   Abstract »    Full Text »    PDF »


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