LTBP-2 Has a Single High-Affinity Binding Site for FGF-2 and Blocks FGF-2-Induced Cell Proliferation
| Autor: | Mahroo K. Parsi, Allison J. Cowin, Clementine Menz, Mark Gibson, Mohamed Arshad Mohamed Sideek, Julian R. J. Adams, Zlatko Kopecki |
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| Přispěvatelé: | Menz, Clementine, Parsi, Mahroo K, Adams, Julian RJ, Sideek, Mohamed A, Kopecki, Zlatko, Cowin, Allison J, Gibson, Mark A |
| Rok vydání: | 2014 |
| Předmět: |
lcsh:Medicine
Plasma protein binding Biology Fibroblast growth factor Fibrillins Cell Line 03 medical and health sciences 0302 clinical medicine medicine Humans Protein Interaction Domains and Motifs Receptor Fibroblast Growth Factor Type 1 Binding site Fibroblast lcsh:Science 030304 developmental biology Cell Proliferation Skin transforming growth factor beta 0303 health sciences Multidisciplinary Binding Sites binding site Heparin lcsh:R Microfilament Proteins enzyme activation Fibroblasts Molecular biology Recombinant Proteins Cell biology Latent TGF-beta binding protein Protein Transport medicine.anatomical_structure Latent TGF-beta Binding Proteins Cell culture 030220 oncology & carcinogenesis Keloid lcsh:Q Fibroblast Growth Factor 2 heparan sulfate Transforming growth factor Protein Binding Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 8, p e0135577 (2015) |
| ISSN: | 1932-6203 |
| Popis: | 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 Refereed/Peer-reviewed |
| Databáze: | OpenAIRE |
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