Insulin-like growth factor binding protein proteolysis

• Published in: Trends in endocrinology and metabolism 2003-05, Vol.14 (4), p.176-181
• Main Authors: Clay Bunn, R., Fowlkes, John L.
• Format: Article
• Language: English
• Subjects: Animals; Apud cells. Peptide and protein hormones. Growth factors; Biological and medical sciences; Endopeptidases - metabolism; Fundamental and applied biological sciences. Psychology; Humans; Insulin-Like Growth Factor Binding Proteins - metabolism; Receptor, IGF Type 1 - metabolism; Receptor, IGF Type 2 - metabolism; Receptors, Somatomedin - metabolism; Somatomedins - metabolism; Vertebrates: endocrinology
• ISSN: 1043-2760; 1879-3061
• DOI: 10.1016/S1043-2760(03)00049-3

High-affinity interactions between insulin-like growth factors (IGF-I and IGF-II) and insulin-like growth factor-binding proteins (IGFBP-1, -2, -3, -4, -5 and -6) antagonize the binding of IGF to the type 1 IGF receptor. Proteases found in a variety of biological fluids can degrade IGFBP 1–6 into fragments that have a greatly reduced affinity for IGF-I and IGF-II, increasing the concentration of free IGFs at the cell surface and allowing IGFs to bind to and activate the IGF receptor. Therefore, IGFBP proteolysis directly modulates the first step in IGF receptor signaling and thereby indirectly modulates cell survival, mitogenesis and differentiation. Our understanding of IGFBP proteolysis has grown exponentially over the past five years, with the identification of several new IGFBP proteases, a growing appreciation of the potential for IGF-independent actions of IGFBP fragments and the realization that perturbations of IGFBP proteolysis are seen in, and might contribute to, several pathological conditions.