The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

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

På svenska

Author

  • C Moali
  • B Font
  • F Ruggiero
  • D Eichenberger
  • P Rousselle
  • V Francois
  • Åke Oldberg
  • L Bruckner-Tuderman
  • D J S Hulmes

Summary, in English

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 gamma 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.

Department/s

  • Åke Oldberg´s group

Publishing year

2005

Language

English

Pages

24188-24194

Publication/Series

Journal of Biological Chemistry

Volume

280

Issue

25

Document type

Journal article

Publisher

American Society for Biochemistry and Molecular Biology

Topic

  • Basic Medicine

Status

Published

Research group

  • Åke Oldberg´s group

ISBN/ISSN/Other

  • ISSN: 1083-351X