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

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.

• Authors: Sanjida Ahmed, Kazuhiro Yamamoto, Yuichiro Sato, Takashi Ogawa, Andreas Herrmann, Shouichi Higashi, Kaoru Miyazaki
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 310 Issue 2 Pg. 612-8 (Oct 17 2003) ISSN: 0006-291X [Print] United States
• PMID: 14521955 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

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