Proteolysis of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in 150-kilodalton IGFBP complexes by a cation-dependent protease activity in adult rat serum promotes the release of bound IGF-I

Endocrinology
C Y Lee, M M Rechler

Abstract

Insulin-like growth factor I (IGF-I) circulates in plasma predominantly in a 150-kDa complex together with IGF-binding protein-3 (IGFBP-3), an approximately 40-kDa glycoprotein that binds IGF-I with high affinity, and an 85-kDa acid-labile subunit that does not bind IGFs. The 150-kDa complex serves as a potential reservoir of IGF-1 by sequestering the growth factor in the vascular compartment. Before IGF-I can reach the tissues, however, it must be released from the complex in a form that can cross the capillary-endothelial barrier. The present study demonstrates that proteolysis of IGFBP-3 in the 150-kDa complex occurs in vitro and results in the release of IGF-I. Specific IGFBP-3 protease activity in adult rat serum was demonstrated by incubating the serum at 37 C in the presence and absence of various protease inhibitors, followed by ligand blotting. Intact and truncated (30-kDa) IGFBP-3 were almost completely proteolyzed after 12 h of incubation, whereas IGFBP-2 and IGFBP-4 in the serum were unchanged even after 48-h incubation. The IGFBP-3 protease activity was inhibited by EDTA, indicating cation dependence, and by 4-(2-aminoethyl)-benzenesulfonyl fluoride, a serine protease inhibitor. Fractionation of the serum after inc...Continue Reading

Citations

Aug 7, 2002·International Journal of Cardiology·Marijke BrinkPatrick Delafontaine
Aug 3, 2006·The European Journal of Neuroscience·Yi-Ping YanRobert J Dempsey
Dec 12, 2001·Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society·M S LewittG A Bobek
Oct 18, 2000·Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society·B A BoothR S Bar
Jul 2, 2005·Journal of Pediatric Gastroenterology and Nutrition·Andrew G HallAnthony F Philipps
Dec 19, 2019·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Nobuto KanekoMunetaka Shimizu
Oct 24, 2017·Frontiers in Cardiovascular Medicine·Francesco AngeliniIsotta Chimenti
Aug 4, 1998·The American Journal of Physiology·P G CampbellD R Powell
Dec 21, 2005·The Journal of Biological Chemistry·Bing WangGuo-Ping Shi

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