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- Title
Specific cleavage of insulin-like growth factor-binding protein-1 by a novel protease activity.
- Authors
Wang, J.; Shafqat, J.; Hall, K.; Ståhlberg, M.; Wivall-Helleryd, I.-L.; Bouzakri, K.; Zierath, J. R.; Brismar, K.; Jörnvall, H.; Lewitt, M. S.
- Abstract
Insulin-like growth factor-binding protein-1 (IGFBP-1) is secreted in a highly phosphorylated form that binds IGF-I with high affinity and is resistant to proteolysis. We have purified IGFBP-1-specific protease activity from the urine of an individual with multiple myeloma. This protease efficiently cleaves both phosphorylated and non-phosphorylated IGFBP-1 at Ile130-Ser131, generating fragments that together have higher association and dissociation rates for IGFs compared with intact IGFBP-1. The proteolytic fraction contained azurocidin, a protease homologue hitherto considered inactive. After cleavage of IGFBP-1, there was a lower affinity, but higher capacity for IGF-I binding, suggesting both N- and C-terminal fragments may interact with ligand independently. There was decreased inhibition of IGF-II-stimulated cell growth and glucose uptake. Alone, proteolysed IGFBP-1 stimulated glucose uptake in muscle. We conclude that specific cleavage of IGFBP-1 at target tissues is important in cellular growth and metabolism and opens novel strategies for targeting IGFBP-1 in treatment of disease.
- Subjects
INSULIN-like growth factor-binding proteins; PROTEOLYSIS; METABOLISM; PROTEINASES; MULTIPLE myeloma; TARGET organs (Anatomy); THERAPEUTICS
- Publication
Cellular & Molecular Life Sciences, 2006, Vol 63, Issue 19/20, p2405
- ISSN
1420-682X
- Publication type
Article
- DOI
10.1007/s00018-006-6248-7