HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 25, 22331-22340, June 20, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/25/22331    most recent M302781200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chesneau, V. Articles by Blobel, C. P. Search for Related Content PubMed PubMed Citation Articles by Chesneau, V. Articles by Blobel, C. P. Social Bookmarking                      What's this?

Catalytic Properties of ADAM19^*

Valérie Chesneau , J. David Becherer , Yufang Zheng  ¶, Hediye Erdjument-Bromage ||, Paul Tempst || and Carl P. Blobel  **

From the Cellular Biochemistry and Biophysics Program, ^||Molecular Biology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, the Department of Biochemical and Analytical Pharmacology, GlaxoSmithKline, Research Triangle Park, North Carolina 27709, and ^¶Graduate Program in Physiology, Biophysics, and Molecular Medicine, Weill Graduate School of Medical Science of Cornell University, New York, New York 10021

ADAMs are membrane-anchored glycoproteins with functions in fertilization, heart development, neurogenesis, and protein ectodomain shedding. Here we report an evaluation of the catalytic activity of recombinantly expressed soluble forms of ADAM19, a protein that is essential for cardiovascular morphogenesis. Proteolytic activity of soluble forms of ADAM19 was first demonstrated by their autocatalytic removal of a purification tag (Myc-His) and their ability to cleave myelin basic protein and the insulin B chain. The metalloprotease activity of ADAM19 is sensitive to the hydroxamic acid-type metalloprotease inhibitor BB94 (batimastat) but not to tissue inhibitors of metalloproteases (TIMPs) 1–3. Moreover, ADAM19 cleaves peptides corresponding to the known cleavage sites of tumor necrosis factor- (TNF–), TNF-related activation-induced cytokine (TRANCE, also referred to as osteoprotegerin ligand), and kit ligand-1 (KL-1) in vitro. Although ADAM19 is not required for shedding of TNF and TRANCE in mouse embryonic fibroblasts, its overexpression in COS-7 cells results in strongly increased TRANCE shedding. This suggests a potential role for ADAM19 in shedding TRANCE in cells where both molecules are highly expressed, such as in osteoblasts. Interestingly, our results also indicate that ADAM19 can function as a negative regulator of KL-1 shedding in both COS-7 cells and mouse embryonic fibroblasts, instead of acting directly on KL-1. The identification of potential in vitro substrates offers the basis for further functional studies of ADAM19 in cells and in mice.

Received for publication, March 18, 2003

^* This work was supported by a grant from GlaxoSmithKline (to C. P. B.), by the Memorial Sloan-Kettering Cancer Center Support Grant NCI-P30-CA-08748, by the Samuel and May Rudin Foundation, and by the DeWitt Wallace Fund. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^** To whom correspondence should be addressed: Cellular Biochemistry and Biophysics Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, Box 368, 1275 York Ave., New York, NY 10021. Tel.: 212-639-2915; Fax: 212-717-3047; E-mail: c-blobel{at}ski.mskcc.org.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. L. Kim, B. Zhang, I. P. Mills, M. E. Milla, K. R. Brunden, and V. M.-Y. Lee Effects of TNF{alpha}-Converting Enzyme Inhibition on Amyloid {beta} Production and APP Processing In Vitro and In Vivo J. Neurosci., November 12, 2008; 28(46): 12052 - 12061. [Abstract] [Full Text] [PDF]

				T. J. Wilson, K. C. Nannuru, M. Futakuchi, A. Sadanandam, and R. K. Singh Cathepsin G Enhances Mammary Tumor-Induced Osteolysis by Generating Soluble Receptor Activator of Nuclear Factor-{kappa}B Ligand Cancer Res., July 15, 2008; 68(14): 5803 - 5811. [Abstract] [Full Text] [PDF]

				E. B. Maryon, S. A. Molloy, and J. H. Kaplan O-Linked Glycosylation at Threonine 27 Protects the Copper Transporter hCTR1 from Proteolytic Cleavage in Mammalian Cells J. Biol. Chem., July 13, 2007; 282(28): 20376 - 20387. [Abstract] [Full Text] [PDF]

				J. H. Bell, A. H. Herrera, Y. Li, and B. Walcheck Role of ADAM17 in the ectodomain shedding of TNF-{alpha} and its receptors by neutrophils and macrophages J. Leukoc. Biol., July 1, 2007; 82(1): 173 - 176. [Abstract] [Full Text] [PDF]

				N. Kawaguchi, K. Horiuchi, J. D. Becherer, Y. Toyama, P. Besmer, and C. P. Blobel Different ADAMs have distinct influences on Kit ligand processing: phorbol-ester-stimulated ectodomain shedding of Kitl1 by ADAM17 is reduced by ADAM19 J. Cell Sci., March 15, 2007; 120(6): 943 - 952. [Abstract] [Full Text] [PDF]

				A. Hikita, I. Yana, H. Wakeyama, M. Nakamura, Y. Kadono, Y. Oshima, K. Nakamura, M. Seiki, and S. Tanaka Negative Regulation of Osteoclastogenesis by Ectodomain Shedding of Receptor Activator of NF-{kappa}B Ligand J. Biol. Chem., December 1, 2006; 281(48): 36846 - 36855. [Abstract] [Full Text] [PDF]

				A. Hikita, Y. Kadono, H. Chikuda, A. Fukuda, H. Wakeyama, H. Yasuda, K. Nakamura, H. Oda, T. Miyazaki, and S. Tanaka Identification of an Alternatively Spliced Variant of Ca2+-promoted Ras Inactivator as a Possible Regulator of RANKL Shedding J. Biol. Chem., December 16, 2005; 280(50): 41700 - 41706. [Abstract] [Full Text] [PDF]

				J.-M. Koh, Y.-S. Lee, C.-H. Byun, E.-J. Chang, H. Kim, Y. H. Kim, H.-H. Kim, and G. S. Kim {alpha}-Lipoic acid suppresses osteoclastogenesis despite increasing the receptor activator of nuclear factor {kappa}B ligand/osteoprotegerin ratio in human bone marrow stromal cells J. Endocrinol., June 1, 2005; 185(3): 401 - 413. [Abstract] [Full Text] [PDF]

				H.-X. Wang, Y.-G. Zhao, H.-M. Wang, Q. Yang, H.-Y. Lin, Q.-X. A. Sang, and C. Zhu Expression of adamalysin 19/ADAM19 in the endometrium and placenta of rhesus monkey (Macaca mulatta) during early pregnancy Mol. Hum. Reprod., June 1, 2005; 11(6): 429 - 435. [Abstract] [Full Text] [PDF]

				N. L. Malinin, S. Wright, P. Seubert, D. Schenk, and I. Griswold-Prenner Amyloid-{beta} neurotoxicity is mediated by FISH adapter protein and ADAM12 metalloprotease activity PNAS, February 22, 2005; 102(8): 3058 - 3063. [Abstract] [Full Text] [PDF]

				Y. Zheng, P. Saftig, D. Hartmann, and C. Blobel Evaluation of the Contribution of Different ADAMs to Tumor Necrosis Factor {alpha} (TNF{alpha}) Shedding and of the Function of the TNF{alpha} Ectodomain in Ensuring Selective Stimulated Shedding by the TNF{alpha} Convertase (TACE/ADAM17) J. Biol. Chem., October 8, 2004; 279(41): 42898 - 42906. [Abstract] [Full Text] [PDF]

				J. Zou, F. Zhu, J. Liu, W. Wang, R. Zhang, C. G. Garlisi, Y.-H. Liu, S. Wang, H. Shah, Y. Wan, et al. Catalytic Activity of Human ADAM33 J. Biol. Chem., March 12, 2004; 279(11): 9818 - 9830. [Abstract] [Full Text] [PDF]

				U. Sahin, G. Weskamp, K. Kelly, H.-M. Zhou, S. Higashiyama, J. Peschon, D. Hartmann, P. Saftig, and C. P. Blobel Distinct roles for ADAM10 and ADAM17 in ectodomain shedding of six EGFR ligands J. Cell Biol., March 1, 2004; 164(5): 769 - 779. [Abstract] [Full Text] [PDF]

				H.-M. Zhou, G. Weskamp, V. Chesneau, U. Sahin, A. Vortkamp, K. Horiuchi, R. Chiusaroli, R. Hahn, D. Wilkes, P. Fisher, et al. Essential Role for ADAM19 in Cardiovascular Morphogenesis Mol. Cell. Biol., January 1, 2004; 24(1): 96 - 104. [Abstract] [Full Text] [PDF]