INSULIN-LIKE-GROWTH-FACTOR BINDING PROTEIN-3 AND PROTEIN-5 FORM SODIUM DODECYL SULFATE-STABLE MULTIMERS

Insulin-like growth factor binding proteins (IGFBPs) are important mod ulators of IGF actions, IGFBP-3 and IGFBP-5 can bind to the extracellu lar matrix of a number of cell types. We now describe a new posttransl ational structural modification of IGFBP-3 and IGFBP-5, which could pl ay a role in determining their localization. We incubated radioiodinat ed forms of all six IGFBPs in the presence of a redox buffer consistin g of 10 mM reduced glutathione and 0.2 mM oxidized glutathione. Under these conditions IGFBP-3 and IGFBP-5, but not the other IGFBPs, formed high molecular weight disulfide-linked multimers. Heparin and a pepti de encompassing the high-affinity heparin-binding site in the C-termin al portion of IGFBP-3 were capable of blocking the multimerization of IGFBP-3. IGFBP-3, but not IGFBP-1, was shown to be able to self-associ ate non-covalently, which could be a requisite first step in the forma tion of covalent multimers, The self-association of IGFBP-3 required t he high-affinity heparin-binding site in the C-terminal portion of the molecule. (C) 1997 Academic Press.