Novel insulin-like growth factor-binding protein proteases : detection and characterization

Sammanfattning: Members of the insulin-like growth factor (IGF) system are known to have an impact on cell differentiation, proliferation and survival, and to be important regulators for nutrient metabolism. The IGF-binding proteins (IGFBP-1 to -6) control the availability of IGFs (IGF-I and IGF-II) to their receptors. In the circulation IGFs and IGFBP-3 or IGFBP-5 can bind an acid-labile subunit (ALS) to form a high molecular mass complex, which constitutes a circulating reservoir of IGFs. Posttranslational modification and binding to cells and extracellular matrix may affect the IGF-dependent effects of IGFBPs. For example highly phosphorylated IGFBP-1, which is increased in catabolic conditions, has a high affinity for, and inhibits the actions of IGF-I. IGFBPs also have IGF-independent effects, through the interaction with cell surface structure or extracellular molecules. For example, the RGD sequence in the C-terminus of IGFBP-1 can interact with a cell surface