LTBP-2 has a single high-affinity binding site for FGF-2 and blocks FGF-2-induced cell proliferation.

Menz, Clementine and K. Parsi, Mahroo and R. J. Adams, Julian and Mohamed Sideek, Mohamed Arshad and Kopecki, Zlatko and J. Cowin, Allison and Gibson, Mark A. (2015) LTBP-2 has a single high-affinity binding site for FGF-2 and blocks FGF-2-induced cell proliferation. PLoS ONE, 10 (8). pp. 1-18. ISSN 1932-6203

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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.

Item Type:	Article (Journal)
Additional Information:	6653/62193
Uncontrolled Keywords:	LTBP-2; Single high-affinity; FGF-2 and blocks FGF-2-induced; cell proliferation.
Subjects:	R Medicine > RB Pathology
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Allied Health Sciences > Department of Physical Rehabilitation Sciences
Depositing User:	Dr Mohamed Arshad Mohamed Sideek
Date Deposited:	25 Feb 2018 23:24
Last Modified:	25 Feb 2018 23:24
URI:	http://irep.iium.edu.my/id/eprint/62193

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