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

J. Beattie, K. Phillips, J. Shand, M. Szymanowska, D.J. Flint, G.J. Allan

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

LanguageEnglish
Pages163-175
Number of pages12
JournalJournal of Molecular Endocrinology
Volume34
DOIs
Publication statusPublished - 2005

Fingerprint

Insulin-Like Growth Factor Binding Protein 5
Insulin-Like Growth Factor Binding Protein 3
Somatomedins
Insulin-Like Growth Factor Binding Proteins
Heparin
Insulin-Like Growth Factor I
Insulin-Like Growth Factor II
Biosensing Techniques
Heparitin Sulfate
Surface Plasmon Resonance
Glycosaminoglycans
Protein Binding
Extracellular Matrix
Breast
Epithelial Cells

Keywords

  • endocrinology
  • insulin growth factor
  • IGF
  • medicine
  • pharmacy
  • molecular recognition characteristics

Cite this

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author = "J. Beattie and K. Phillips and J. Shand and M. Szymanowska and D.J. Flint and G.J. Allan",
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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.; Phillips, K.; Shand, J.; Szymanowska, M.; Flint, D.J.; Allan, G.J.

In: Journal of Molecular Endocrinology, Vol. 34, 2005, p. 163-175.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Molecular recognition characteristics in the insulin-like growth factor (IGF)-insulin-like growth factor binding protein-3/5 (IGFBP-3/5) heparin axis

AU - Beattie, J.

AU - Phillips, K.

AU - Shand, J.

AU - Szymanowska, M.

AU - Flint, D.J.

AU - Allan, G.J.

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

KW - endocrinology

KW - insulin growth factor

KW - IGF

KW - medicine

KW - pharmacy

KW - molecular recognition characteristics

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U2 - 10.1677/jme.1.01656

DO - 10.1677/jme.1.01656

M3 - Article

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EP - 175

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T2 - Journal of Molecular Endocrinology

JF - Journal of Molecular Endocrinology

SN - 0952-5041

ER -