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.
Ahmed
Sanjida
S
Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, 641-12 Maioka-cho, Totsuka-ku, Yokohama 244-0813, Japan.
Yamamoto
Kazuhiro
K
Sato
Yuichiro
Y
Ogawa
Takashi
T
Herrmann
Andreas
A
Higashi
Shouichi
S
Miyazaki
Kaoru
K
D000595:Amino Acid Sequence; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D018969:Insulin-Like Growth Factor Binding Proteins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D053668:Syndecan-1; D053667:Syndecans
D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans; C102529:insulin-like growth factor binding protein-related protein 1; D007334:Insulin-Like Growth Factor I