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Molecular recognition characteristics in the insulin-like growth factor (IGF)-insulin-like growth factor binding protein-3/5 (IGFBP-3/5) heparin axis

Beattie, J. and Phillips, K. and Shand, J. and Szymanowska, M. and Flint, D.J. and Allan, G.J. (2005) Molecular recognition characteristics in the insulin-like growth factor (IGF)-insulin-like growth factor binding protein-3/5 (IGFBP-3/5) heparin axis. Journal of Molecular Endocrinology, 34. pp. 163-175. ISSN 0952-5041

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Abstract

Insulin-like growth factor binding proteins (IGFBPs) -3 and -5 are known to interact with various components of the extracellular matrix (ECM; e.g. heparin and heparan sulphate) and this interaction is believed to affect the affinity of both IGFBP species for their cognate ligands – IGF-I and -II. There is little detail on the nature of the molecular complex formed between ECM components, IGFBPs and IGFs although the glycosaminoglycan (GAG) heparin has been reported to reduce the affinity of IGFBP-5 for IGF-I. In order to investigate this phenomenon further, we have undertaken an extensive surface plasmon resonance based biosensor study to report the affinity of IGFBP-3 and -5 for binding heparin (22 and 7 nM respectively). We have also shown that pre-complexation of IGFBP with IGF-I and -II inhibits the subsequent association of IGFBP with heparin and conversely that heparin complexation of IGFBP-3 and -5 inhibits IGFBP binding to biosensor surfaces containing immobilised IGF-I. In addition we have used both IGF-I and heparin coated biosensor surfaces in an attempt to build ternary IGF–IGFBP–heparin complexes in order to gain some insight into the nature of inhibition by heparin of IGFI–IGFBP complex formation. Our data lead us to conclude that the inhibition by heparin is partly competitive in nature, and that ternary complexes of IGF–IGFBP–heparin are either unable to form, or only form unstable transient complexes. The potential biological significance of our data is highlighted by the demonstration that IGF-I and IGF-II can displace endogenous IGFBP-5 from monolayer cultures of the mouse mammary epithelial cell line HC11.

Item type: Article
ID code: 10443
Keywords: endocrinology, insulin growth factor, IGF, medicine, pharmacy, molecular recognition characteristics, Pharmacy and materia medica, Molecular Biology, Endocrinology
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
    Depositing user: Strathprints Administrator
    Date Deposited: 23 Jun 2011 12:45
    Last modified: 04 Sep 2014 19:40
    URI: http://strathprints.strath.ac.uk/id/eprint/10443

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