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

Biochem Biophys Res Commun. 2003 Oct 17;310(2):612-8. doi: 10.1016/j.bbrc.2003.09.058.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Adhesion / drug effects
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Humans
  • Insulin / metabolism
  • Insulin / pharmacology
  • Insulin-Like Growth Factor Binding Proteins / chemistry
  • Insulin-Like Growth Factor Binding Proteins / metabolism*
  • Insulin-Like Growth Factor Binding Proteins / pharmacology*
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor I / pharmacology
  • Membrane Glycoproteins / metabolism
  • Proteoglycans / metabolism
  • Syndecan-1
  • Syndecans

Substances

  • Insulin
  • Insulin-Like Growth Factor Binding Proteins
  • Membrane Glycoproteins
  • Proteoglycans
  • SDC1 protein, human
  • Syndecan-1
  • Syndecans
  • insulin-like growth factor binding protein-related protein 1
  • Insulin-Like Growth Factor I