Title : Synthesis and characterization of
insulin-like growth
factor-binding protein (
IGFBP)-7
Abstract :
- Recombinant human mac25 protein specifically binds IGF-I and -II
- The mac25 cDNA was originally cloned from leptomeningial cells and subsequently reisolated through differential display as a sequence preferentially expressed in senescent human mammary epithelial cells
- The deduced amino acid sequence of the human mac25 propeptide shares a 20-25% identity to human insulin-like growth factor-binding proteins ( IGFBPs ), suggesting that mac25 could be another member of the IGFBP family
- In the present study, we have generated recombinant human mac25 (rh- mac25 ) in a baculovirus expression system and assessed its affinity for IGFs and have evaluated the pattern of expression of the mac25 gene in human tissues
- Binding of 125I- IGF-I and 125I- IGF-II to rh- mac25 was demonstrated by Western ligand blotting after nondenaturing polyacrylamide gel electrophoresis and by affinity cross-linking with as little as 2 nM rh- mac25
- Specificity of rh- mac25 binding to 125I-IGFs was demonstrated by competition for rh- mac25 binding with unlabeled IGFs, but not with [ QAYLL]IGF-II analog, which has 100-fold less affinity for IGFBPs
- In comparison with IGFBP-3 , rh- mac25 has at least a 5-6-fold lower affinity for IGF-I and 20-25-fold lower affinity for IGF-II
- mac25 mRNA was detectable in a wide range of normal human tissues, with decreased expression in breast, prostate, colon, and lung cancer cell lines
- In conclusion, mac25 specifically binds IGFs and constitutes a new member of the IGFBP family, IGFBP-7
- Its wider distribution in normal tissue and lower expression in several cancer cells indicate that IGFBP-7 may function as a growth-suppressing factor , as well as an IGF-binding protein
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