Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/94663
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Type: | Journal article |
Title: | LTBP-2 has a single high-affinity binding site for FGF-2 and blocks FGF-2-induced cell proliferation |
Author: | Menz, C. Parsi, M. Adams, J. Sideek, M. Kopecki, Z. Cowin, A. Gibson, M. |
Citation: | PLoS One, 2015; 10(8):e0135577-1-e0135577-18 |
Publisher: | Public Library of Science |
Issue Date: | 2015 |
ISSN: | 1932-6203 1932-6203 |
Editor: | Addison, C. |
Statement of Responsibility: | Clementine Menz, Mahroo K. Parsi, Julian R. J. Adams, Mohamed A. Sideek, Zlatko Kopecki, Allison J. Cowin, Mark A. Gibson |
Abstract: | Latent transforming growth factor-beta-1 binding protein-2 (LTBP-2) belongs to the fibrillin-LTBP superfamily of extracellular matrix proteins. LTBPs and fibrillins are involved in the sequestration and storage of latent growth factors, particularly transforming growth factor β (TGF-β), in tissues. Unlike other LTBPs, LTBP-2 does not covalently bind TGF-β, and its molecular functions remain unclear. We are screening LTBP-2 for binding to other growth factors and have found very strong saturable binding to fibroblast growth factor-2 (FGF-2) (Kd = 1.1 nM). Using a series of recombinant LTBP-2 fragments a single binding site for FGF-2 was identified in a central region of LTBP-2 consisting of six tandem epidermal growth factor-like (EGF-like) motifs (EGFs 9-14). This region was also shown to contain a heparin/heparan sulphate-binding site. FGF-2 stimulation of fibroblast proliferation was completely negated by the addition of 5-fold molar excess of LTBP-2 to the assay. Confocal microscopy showed strong co-localisation of LTBP-2 and FGF-2 in fibrotic keloid tissue suggesting that the two proteins may interact in vivo. Overall the study indicates that LTBP-2 is a potent inhibitor of FGF-2 that may influence FGF-2 bioactivity during wound repair particularly in fibrotic tissues. |
Keywords: | Cell Line Fibroblasts Skin Humans Keloid Microfilament Proteins Heparin Fibroblast Growth Factor 2 Recombinant Proteins Cell Proliferation Binding Sites Protein Binding Protein Transport Receptor, Fibroblast Growth Factor, Type 1 Latent TGF-beta Binding Proteins Protein Interaction Domains and Motifs Fibrillins |
Rights: | © 2015 Menz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
DOI: | 10.1371/journal.pone.0135577 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/519211 |
Published version: | http://dx.doi.org/10.1371/journal.pone.0135577 |
Appears in Collections: | Aurora harvest 3 Medicine publications |
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hdl_94663.pdf | Published version | 11.79 MB | Adobe PDF | View/Open |
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