Abstract
Insulin-like growth factor binding protein-3 (IGFBP-3) binds IGF-I and IGF-II with high affinity, at least an order of magnitude higher than the affiniy of the IGFs for the IGFIR. It has been hypothesized that IGFBP-3 inhibits IGF binding to the IGFIR via a mechanism independent of its ability to sequester IGFs. In the present study, we examined the effects of IGFBP-3 and its proteolytic fragments on the initial events of the IGFIR signalling pathway. IGFBP-3 inhibited IGF-I-, IGF-II-, Des(1-3)IGF-I- and Long(R3)IGF-I-induced IGFIR phosphorylation in a dose-dependent manner at similar concentration range but not QAYL-induced IGFIR-P. The (1-97)IGFBP-3 fragment was able to inhibit only IGF-I-induced IGFIR-P. The (1-97)IGFBP-3 fragment but not intact IGFBP-3 inhibited insulin-induced IGFIR-P. Monolayer cross-linking with [125I]IGFBP-3 indicated that there is no direct interaction of IGFBP-3 with the IGFIR. This study demonstrates that the effect on the initial step of IGFIR signalling by IGFBP-3 is largely due to its ability to sequester IGF and the IGF analogues in the extracellular milieu and not the result of any interaction of IGFBP-3 with the IGFIR or a mechanism independent of its ability to bind IGFs.
Original language | English (US) |
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Pages (from-to) | 231-239 |
Number of pages | 9 |
Journal | Growth Hormone and IGF Research |
Volume | 11 |
Issue number | 4 |
DOIs | |
State | Published - Aug 2001 |
Keywords
- Des-IGF-I
- IGF-I receptor signalling
- IGFBP-3
- IGFBP-3 proteolysis
- Long-R3-IGF-I
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Endocrinology