Comparative Binding of Neurotrophins (NT-3, CNTF and NGF) and Various Cytokines to α₂-Macroglobulin

All the nine common cytokines in this study (including NT-3, IGF-1, CNTF and TGF-α) bind noncovalently, yet with different specificities and to different degrees, with both normal α₂-macroglobulin (α₂M) and monoamine-modified α₂M. The binding of NGF is by far the most efficient and is least affected by cationic proteins. The binding of NT-3 is slightly affected by cationic proteins but is completely blocked by NGF. The binding of TGF-α, TGF-β₁, CNTF, and IL-6 is severely blocked by cationic proteins/NGF. We conclude that NGF and NT-3 appear to bind specifically in significant quantities to the same α₂M sites; but the other cytokines by comparison bind minimally, and primarily or entirely use nonspecific molecular interactions in their binding to α₂M.