Insulin-like growth factor (IGF)-binding protein-5-(201-218) region regulates hydroxyapatite and IGF-I binding.
Insulin-like growth factor-binding protein-5 (IGFBP-5), the major bone IGFBP, modifies the biological activity of IGFs within the osteoblastic pericellular environment. Because glycosaminoglycans modulate IGFBP-5 binding to osteoblast organic extracellular matrix (ECM), we assessed whether the heparin binding domain of IGFBP-5, IGFBP-5-(102-218), modifies the interaction of IGFBP-5 with the inorganic bone ECM hydroxyapatite (HA). Synthetic IGFBP-5-(201-218) peptide increased the binding of IGFBP-5 to HA as well as the binding of IGF-I to HA-bound IGFBP-5. This action was specific for the heparin-binding domain, because IGFBP-5-(130-138), IGFBP-5-(138-152), and IGFBP-5-(1-169) were without effect. IGFBP-5-(201-218) was found to bind directly to IGFBP-5 and cause a threefold enhancement of the IGF-I binding affinity for IGFBP-5, whether IGFBP-5 was bound to HA or was in a matrix-free fluid phase. Heparin inhibited the binding of IGFBP-5 to HA and blocked the interaction of IGFBP-5 with IGFBP-5-(201-218) in the fluid phase, suggesting that the primary heparin-binding domain of IGFBP-5 specifically enhances the binding of IGFBP-5 to HA and increases IGF-I binding to IGFBP-5.
Campbell
P G
PG
Orthopaedic Research Laboratory, Allegheny University of the Health Sciences, Pittsburgh, Pennsylvania 15212, USA.
Andress
D L
DL
D000595:Amino Acid Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D017886:Durapatite / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism; D006801:Humans; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000378:metabolism* / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007700:Kinetics; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000378:metabolism
D018975:Insulin-Like Growth Factor Binding Protein 5; D010446:Peptide Fragments; D011994:Recombinant Proteins; C109256:insulin-like growth factor binding protein 5 (201-218); D007334:Insulin-Like Growth Factor I; D006493:Heparin; D017886:Durapatite