| Added by | standudu |
|---|---|
| Last modified by | liaudet-coopman |
| Group name | EquipeELC |
| Item Type | Journal Article |
| Title | Proteolytic control of TGF-? co-receptor activity by BMP-1/tolloid-like proteases revealed by quantitative iTRAQ proteomics |
| Creator | Delolme et al. |
| Author | Frédéric Delolme |
| Author | Cyril Anastasi |
| Author | Lindsay B. Alcaraz |
| Author | Valentin Mendoza |
| Author | Sandrine Vadon-Le Goff |
| Author | Maya Talantikite |
| Author | Robin Capomaccio |
| Author | Jimmy Mevaere |
| Author | Laëtitia Fortin |
| Author | Dominique Mazzocut |
| Author | Odile Damour |
| Author | Isabelle Zanella-Cléon |
| Author | David J. S. Hulmes |
| Author | Christopher M. Overall |
| Author | Ulrich Valcourt |
| Author | Fernando Lopez-Casillas |
| Author | Catherine Moali |
| Abstract | The metalloproteinase BMP-1 (bone morphogenetic protein-1) plays a major role in the control of extracellular matrix (ECM) assembly and growth factor activation. Most of the growth factors activated by BMP-1 are members of the TGF-? superfamily known to regulate multiple biological processes including embryonic development, wound healing, inflammation and tumor progression. In this study, we used an iTRAQ (isobaric tags for relative and absolute quantification)-based quantitative proteomic approach to reveal the release of proteolytic fragments from the cell surface or the ECM by BMP-1. Thirty-eight extracellular proteins were found in significantly higher or lower amounts in the conditioned medium of HT1080 cells overexpressing BMP-1 and thus, could be considered as candidate substrates. Strikingly, three of these new candidates (betaglycan, CD109 and neuropilin-1) were TGF-? co-receptors, also acting as antagonists when released from the cell surface, and were chosen for further substrate validation. Betaglycan and CD109 proved to be directly cleaved by BMP-1 and the corresponding cleavage sites were extensively characterized using a new mass spectrometry approach. Furthermore, we could show that the ability of betaglycan and CD109 to interact with TGF-? was altered after cleavage by BMP-1, leading to increased and prolonged SMAD2 phosphorylation in BMP-1-overexpressing cells. Betaglycan processing was also observed in primary corneal keratocytes, indicating a general and novel mechanism by which BMP-1 directly affects signaling by controlling TGF-? co-receptor activity. The proteomic data have been submitted to ProteomeXchange with the identifier PXD000786 and doi: 10.6019/PXD000786 . |
| Publication | Cellular and molecular life sciences: CMLS |
| Volume | 72 |
| Issue | 5 |
| Pages | 1009-1027 |
| Date | Mar 2015 |
| Journal Abbr | Cell. Mol. Life Sci. |
| Language | eng |
| DOI | 10.1007/s00018-014-1733-x |
| ISSN | 1420-9071 |
| Library Catalog | PubMed |
| Extra | PMID: 25260970 |
| Tags | Antigens, CD, Bone Morphogenetic Protein 1, Cell Line, Tumor, Chromatography, High Pressure Liquid, first-last-corresponding, GPI-Linked Proteins, Humans, Neoplasm Proteins, Neuropilin-1, original, Peptides, Phosphorylation, Protein Binding, Proteolysis, Receptors, Transforming Growth Factor beta, Signal Transduction, Smad2 Protein, Spectrometry, Mass, Electrospray Ionization, Transforming Growth Factor beta |
| Date Added | 2019/05/28 - 17:28:09 |
| Date Modified | 2019/05/29 - 12:24:30 |
| Notes and Attachments | PubMed entry (Attachment) |
Institut de Recherche en Cancérologie de
