GORDON, RE; DUAN, C: Glycosylated and non-glycosylated insulin-like growth factor binding protein-5 (IGFBP-5) have different biological actions

IGFBP-5 has been shown to either inhibit or potentiate IGF actions by modulating the IGF ligand and receptor interaction. IGFBP-5 has also been shown to have intrinsic biological activity that is ligand-independent. The molecular mechanism underlying this dual functionality of IGFBP-5 is not clear. IGFBP-5 is normally found as a characteristic doublet of 29-31 kDa from both cellular and plasma sources. These two natural forms of IGFBP-5 are two differentially glycosylated variants. To determine whether glycosylation affects IGFBP-5 function, we examined the biological effects of glycosylated and non-glycosylated IGFBP-5. Both glycosylated and non-glycosylated IGFBP-5 bind to IGFs with high affinity. When added to the cells alone, glycosylated, but not non-glycosylated, IGFBP-5, significantly stimulated cell migration. This effect is independent from the endogenous IGF-I. The effects of the two forms of IGFBP-5 on cell proliferation were examined by BrdU labeling. When added to cells alone, neither non-glycosylated nor glycosylated IGFBP-5 caused any significant changes in cell proliferation. Co-incubation of either non-glycosylated or glycosylated IGFBP-5 with IGF-I, at an equal molar ratio, resulted in an increase in the IGF-I-stimulated cell proliferation. This action is ligand-dependent since no such potentiation effect was observed when incubated IGFBP-5 with Des(1-3)IGF-I, an IGF analogue with impaired affinity for IGFBP-5. These data suggest that while both forms of IGFBP-5 bind IGFs with high affinity and modulate IGF action on cell proliferation, only the glycosylated IGFBP-5 regulate cell motility via an IGF-independent mechanism. Therefore, the dual functionality of IGFBP-5 may be attributed to its differential glycosylation states (Supported by NIHRO1HL60679).