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

J. Biol. Chem., Vol. 279, Issue 5, 3726-3732, January 30, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/5/3726    most recent M309342200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Angeloni, D. Articles by Lerman, M. I. Search for Related Content PubMed PubMed Citation Articles by Angeloni, D. Articles by Lerman, M. I. Social Bookmarking                      What's this?

The Soluble Sema Domain of the RON Receptor Inhibits Macrophage-stimulating Protein-induced Receptor Activation^*

Debora Angeloni¶, Alla Danilkovitch-Miagkova¶||, Alexei Miagkov**, Edward J. Leonard, and Michael I. Lerman

From the Laboratory of Immunobiology, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702-1201

RON is a receptor tyrosine kinase of the MET family that is involved in cell proliferation, cell survival, and cell motility in both normal and disease states. Macrophage-stimulating protein (MSP) is the RON ligand whose binding to RON causes receptor activation. RON is a trans-membrane heterodimer comprised of one - and one -chain originating from a single-chain precursor and held together by several disulfide bonds. The intracellular part of RON contains the kinase domain and regulatory elements. The extracellular region is characterized by the presence of a sema domain (a stretch of 500 amino acids with several highly conserved cysteine residues), a PSI (plexin, semaphorins, integrins) domain, and four immunoglobulin-like folds. Here we show that a soluble, secreted molecule representing the sema domain of RON (referred to as ron-sema) has a dominant negative effect on the ligand-induced receptor activation and is capable of inhibiting RON-dependent signaling pathways and cellular responses. Results suggest that the sema domain of RON participates in ligand binding by the full-length receptor. The ability of ron-sema to suppress growth of MSP-responsive cells in culture, including cancer cells, points to a potential therapeutic use of this molecule, and forced expression of it could potentially be used as a gene therapy tool for treating MSP-dependent types of cancer.

Received for publication, August 22, 2003 , and in revised form, October 29, 2003.

^* This work was supported by NCI, National Institutes of Health Contract NO1-CO-56000. 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.

Present address: Scuola Superiore Sant'Anna and Istituto di Fisiologia Clinica-Consiglio Nazionale delle Richerche, 56100 Pisa, Italy.

^¶ Both authors contributed equally to the work.

^|| Present address: Osiris Therapeutics, Inc., 2001 Aliceanna St., Baltimore, MD 21231.

^** Neuromuscular Research Laboratory, Johns Hopkins School of Medicine, Baltimore, MD 21287-7519.

To whom correspondence should be addressed: Laboratory of Immunobiology, NCI, National Institutes of Health, Bldg. 560, Rm. 12-68, Frederick, MD 21702-1201. Tel.: 301-846-7323; Fax: 301-846-6145; E-mail: lerman{at}ncifcrf.gov.

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

This article has been cited by other articles:

				J. M. O'Toole, K. E. Rabenau, K. Burns, D. Lu, V. Mangalampalli, P. Balderes, N. Covino, R. Bassi, M. Prewett, K. J. Gottfredsen, et al. Therapeutic Implications of a Human Neutralizing Antibody to the Macrophage-Stimulating Protein Receptor Tyrosine Kinase (RON), a c-MET Family Member. Cancer Res., September 15, 2006; 66(18): 9162 - 9170. [Abstract] [Full Text] [PDF]

				E. R. Camp, W. Liu, F. Fan, A. Yang, R. Somcio, and L. M. Ellis RON, a Tyrosine Kinase Receptor Involved in Tumor Progression and Metastasis Ann. Surg. Oncol., April 1, 2005; 12(4): 273 - 281. [Abstract] [Full Text] [PDF]

				D. Kirchhofer, X. Yao, M. Peek, C. Eigenbrot, M. T. Lipari, K. L. Billeci, H. R. Maun, P. Moran, L. Santell, C. Wiesmann, et al. Structural and Functional Basis of the Serine Protease-like Hepatocyte Growth Factor {beta}-Chain in Met Binding and Signaling J. Biol. Chem., September 17, 2004; 279(38): 39915 - 39924. [Abstract] [Full Text] [PDF]