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

J. Biol. Chem., Vol. 280, Issue 25, 24188-24194, June 24, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/25/24188    most recent M501486200v1 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 Moali, C. Articles by Hulmes, D. J. S. Search for Related Content PubMed PubMed Citation Articles by Moali, C. Articles by Hulmes, D. J. S. Social Bookmarking                      What's this?

Substrate-specific Modulation of a Multisubstrate Proteinase

C-TERMINAL PROCESSING OF FIBRILLAR PROCOLLAGENS IS THE ONLY BMP-1-DEPENDENT ACTIVITY TO BE ENHANCED BY PCPE-1^*

Catherine Moali, Bernard Font, Florence Ruggiero, Denise Eichenberger, Patricia Rousselle, Vincent François, Åke Oldberg¶, Leena Bruckner-Tuderman||, and David J. S. Hulmes**

From the IFR 128 Biosciences Lyon-Gerland, Institut de Biologie et Chimie des Protéines, CNRS/UCBL1 UMR 5086, 69367 Lyon cedex 7, France, the Institut de Génétique Humaine, CNRS UPR1142, 34396 Montpellier cedex 5, France, the ^¶Department of Cell and Molecular Biology, University of Lund, S-221 00 Lund, Sweden, and the ^||Department of Dermatology, University of Freiburg, 79104 Freiburg, Germany

Members of the bone morphogenetic protein-1/tolloid (BMP-1/Tld) family of metalloproteinases, also known as procollagen C-proteinases (PCPs), control multiple biological events (including matrix assembly, cross-linking, cell adhesion/migration and pattern formation) through enzymatic processing of several extracellular substrates. PCP activities on fibrillar procollagens can be stimulated by another family of extracellular proteins, PCP enhancers (PCPE-1, PCPE-2), which lack intrinsic enzymatic activity. While PCPs have multiple substrates, the extent to which PCPEs is involved in the processing of proteins other than fibrillar procollagens is unknown. In the experiments reported here, PCPE-1 was found to have no effect on the in vitro BMP-1 processing of procollagen VII, the procollagen V N-propeptide, the laminin 5 2 chain, osteoglycin, prolysyl oxidase, or chordin. In contrast, PCPE-1 enhanced C-terminal processing of human fibrillar procollagen III but only when this substrate was in its native, disulfide-bonded conformation. Surprisingly, processing of procollagen III continued to be enhanced when essentially all the triple-helical region was removed. These and previous results (Ricard-Blum, S., Bernocco, S., Font, B., Moali, C., Eichenberger, D., Farjanel, J., Burchardt, E. R., van der Rest, M., Kessler, E., and Hulmes, D. J. S. (2002) J. Biol. Chem. 277, 33864-33869; Bernocco, S., Steiglitz, B. M., Svergun, D. I., Petoukhov, M. V., Ruggiero, F., Ricard-Blum, S., Ebel, C., Geourjon, C., Deleage, G., Font, B., Eichenberger, D., Greenspan, D. S., and Hulmes, D. J. S. (2003) J. Biol. Chem. 278, 7199-7205) indicate that the mechanism of PCPE-1 action involves recognition sites in both the C-propeptide domain and in the C-telopeptide region of the procollagen molecule. PCPEs therefore define a new class of extracellular adaptor proteins that stimulate proteinase activity in a substrate-specific manner, thereby providing a new target for the selective regulation of PCP activity on fibrillar procollagen substrates.

Received for publication, February 8, 2005 , and in revised form, April 6, 2005.

^* This work was supported by the Région Rhône-Alpes, the European Commission (contract no. NMP2-CT-2003-504017), the Ligue Contre le Cancer, the Association pour la Recherche sur le Cancer, Coletica (Lyon, France), the Centre National de la Recherche Scientifique, and the Université Claude Bernard Lyon 1. 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: IBCP, 7 Passage du Vercors, 69367 Lyon cedex 7, France. Tel.: 33-472722667; Fax: 33-472722604; E-mail: d.hulmes{at}ibcp.fr.

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

This article has been cited by other articles:

				T. J. Geach and L. Dale Molecular Determinants of Xolloid Action in Vivo J. Biol. Chem., October 3, 2008; 283(40): 27057 - 27063. [Abstract] [Full Text] [PDF]

				M. Tran, P. Rousselle, P. Nokelainen, S. Tallapragada, N. T. Nguyen, E. F. Fincher, and M. P. Marinkovich Targeting a Tumor-Specific Laminin Domain Critical for Human Carcinogenesis Cancer Res., April 15, 2008; 68(8): 2885 - 2894. [Abstract] [Full Text] [PDF]

				G. Blanc, B. Font, D. Eichenberger, C. Moreau, S. Ricard-Blum, D. J. S. Hulmes, and C. Moali Insights into How CUB Domains Can Exert Specific Functions while Sharing a Common Fold: CONSERVED AND SPECIFIC FEATURES OF THE CUB1 DOMAIN CONTRIBUTE TO THE MOLECULAR BASIS OF PROCOLLAGEN C-PROTEINASE ENHANCER-1 ACTIVITY J. Biol. Chem., June 8, 2007; 282(23): 16924 - 16933. [Abstract] [Full Text] [PDF]

				G. Ge, Y. Zhang, B. M. Steiglitz, and D. S. Greenspan Mammalian Tolloid-like 1 Binds Procollagen C-proteinase Enhancer Protein 1 and Differs from Bone Morphogenetic Protein 1 in the Functional Roles of Homologous Protein Domains J. Biol. Chem., April 21, 2006; 281(16): 10786 - 10798. [Abstract] [Full Text] [PDF]

				B. M. Steiglitz, J. M. Kreider, E. P. Frankenburg, W. N. Pappano, G. G. Hoffman, J. A. Meganck, X. Liang, M. Hook, D. E. Birk, S. A. Goldstein, et al. Procollagen C Proteinase Enhancer 1 Genes Are Important Determinants of the Mechanical Properties and Geometry of Bone and the Ultrastructure of Connective Tissues Mol. Cell. Biol., January 1, 2006; 26(1): 238 - 249. [Abstract] [Full Text] [PDF]