Insulin-like growth factor (IGF)-binding protein 5 forms an alternative ternary complex with IGFs and the acid-labile subunit.
Up to 90% of circulating insulin-like growth factors (IGF-I and IGF-II) are carried in heterotrimeric complexes with a binding protein (IGFBP) and a liver-derived glycoprotein known as the acid-labile subunit. IGFBP-3 is considered unique among the six well characterized IGFBPs in its ability to complex with the acid-labile subunit. However, a basic carboxyl-terminal domain of IGFBP-3, known to be involved in its interaction with the acid-labile subunit, is shared by IGFBP-5, suggesting the possibility of ternary complexes containing IGFBP-5. We now demonstrate using three independent methods that human IGFBP-5, when occupied by IGF-I or IGF-II, forms ternary complexes of approximately 130 kDa with the acid-labile subunit. IGFBP-3 competes with approximately twice the potency of IGFBP-5 for the formation of such complexes. No other IGFBP complexes with the acid-labile subunit itself or competes with IGFBP-5 for complex formation. As observed for IGFBP-3, ternary complexes containing IGFBP-5 form preferentially in the presence of IGF-I, even though IGFBP-5 has a preferential affinity for IGF-II over IGF-I. By size fractionation chromatography, serum IGFBP-5 co-elutes predominantly with ternary complexes. The demonstration of IGFBP-5-containing ternary complexes indicates an unrecognized form of IGF transport in the circulation and an additional mechanism for regulating IGF bioavailability.
Twigg
S M
SM
Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia.
Baxter
R C
RC
D001667:Binding, Competitive; D002352:Carrier Proteins / Q000378:metabolism*; D003432:Cross-Linking Reagents; D004591:Electrophoresis, Polyacrylamide Gel; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding
D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D006023:Glycoproteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D018975:Insulin-Like Growth Factor Binding Protein 5; C075944:insulin-like growth factor binding protein, acid labile subunit; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II