LTBP-2 has a single high-affinity binding site for FGF-2 and blocks FGF-2-induced cell proliferation.
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....
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English English |
| Published: |
Public Library of Science
2015
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| Subjects: | |
| Online Access: | http://irep.iium.edu.my/62193/1/LTBP-2%20FGF-2%20paper%20-%20PLOS%20One.pdf http://irep.iium.edu.my/62193/7/62193_LTBP-2%20has%20a%20single%20high-affinity%20binding_scopus.pdf http://irep.iium.edu.my/62193/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4532469/pdf/pone.0135577.pdf |
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| Summary: | 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. |
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