Formation of 150-kDa binary complexes of insulin-like growth factor binding protein-3 and the acid-labile subunit in vitro and in vivo.
Adult rat serum contains two types of 150-kDa IGFBP complexes: ternary complexes containing bound IGF-I, intact IGFBP-3 and the acid-labile subunit (ALS), and binary complexes that contain ALS and proteolytically-nicked IGFBP-3 but which lack bound IGF. We present evidence that the binary complexes containing proteolytically-nicked IGFBP-3 can be formed in two ways: by direct association of IGFBP-3 with ALS in the absence of IGF, and by proteolysis of IGFBP-3 within 150-kDa ternary complexes, resulting in increased dissociation of IGF-I. The relative contributions of the two mechanisms is unknown. Preliminary results indicate that binary complexes also can form in vivo. Proteolysis of IGFBP-3 in the 150-kDa ternary complex provides a regulatable mechanism by which IGF-I may be mobilized from the circulating reservoir of 150-kDa complexes to the tissues.
Lee
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CY
Growth and Development Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1758, USA.
Rechler
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MM
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D066298:In Vitro Techniques; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008970:Molecular Weight; D011487:Protein Conformation; D051381:Rats; D013002:Somatomedins / Q000378:metabolism*
D002352:Carrier Proteins; D006023:Glycoproteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D013002:Somatomedins; C075944:insulin-like growth factor binding protein, acid labile subunit; D007334:Insulin-Like Growth Factor I; D010450:Endopeptidases; C080473:insulin-like growth factor binding protein-3 protease