Proteolytic processing of IGFBP-related protein-1 (TAF/angiomodulin/mac25) modulates its biological activity.

Insulin-like growth factor (IGF) binding protein-related protein-1 (IGFBP-rP1) was previously identified as tumor-derived adhesion factor (TAF) secreted from human bladder carcinoma cells. It exhibits growth-stimulatory activity in synergy with insulin or IGFs. In the present study, we found that IGFBP-rP1 was proteolytically cleaved to a two-chain form. The cleavage sequence suggested that a trypsin-like serine proteinase may be responsible for the processing. The cleavage of IGFBP-rP1 led to an almost complete loss of both insulin/IGF-1-binding activity and insulin/IGF-1-dependent growth-stimulatory activity. On the other hand, the cell attachment activity of IGFBP-rP1 was markedly increased by the proteolytic processing. Syndecan-1 was thought to be a cell surface receptor for both intact and cleaved IGFBP-rP1 forms. Although the proteolytic cleavage of IGFBP-rP1 decreased its heparin-binding activity, the cleaved form could bind syndecan-1 efficiently. Thus the proteolytic processing of IGFBP-rP1 seems to modulate its insulin/IGF-dependent and -independent biological functions.