Regulation of Insulin-like Growth Factor (IGF) Activity by Insulin-like Growth Factor Binding Proteins (IGFBPs) (Homo sapiens)
About 75% of circulating IGFs are in 1500 220 KDa complexes with IGFBP 3 and ALS. Such complexes are too large to pass the endothelial barrier. The remaining 20 25% of IGFs are bound to other IGFBPs in 40 50 KDa complexes. IGFs are released from IGF:IGFBP complexes by proteolysis of the IGFBP. IGFs become active after release, however IGFs may also have activity when still bound to some IGFBPs. IGFBP 1 is enriched in amniotic fluid and is produced in the liver under control of insulin (insulin suppresses production). IGFBP 1 binding stimulates IGF function. It is unknown which if any protease degrades IGFBP 1. IGFBP 2 is enriched in cerebrospinal fluid; its binding inhibits IGF function. IGFBP 2 is not significantly degraded in circulation. IGFBP 3, which binds most IGF in the body is enriched in follicular fluid and found in many other tissues. IGFBP 3 may be cleaved by plasmin, thrombin, Prostate specific Antigen (PSA), Matrix Metalloprotease 1, and Matrix Metalloprotease 2. IGFBP 3 also binds extracellular matrix and binding lowers its affinity for IGFs. IGFBP 3 binding stimulates the effects of IGFs. IGFBP 4 acts to inhibit IGF function and is cleaved by Pregnancy associated Plasma Protein A (PAPP A) to release IGF. IGFBP 5 is enriched in bone matrix; its binding stimulates IGF function. IGFBP 5 is cleaved by Pregnancy Associated Plasma Protein A2 (PAPP A2), ADAM 9, complement C1s from smooth muscle, and thrombin. Only the cleavage site for PAPP A2 is known.IGFBP 6 is enriched in cerebrospinal fluid. It is unknown which if any protease degrades IGFBP 6.
View all 37...
|Cathepsin G||Protein||P08311 (UniProt)|
|PAPP-A and PAPP-A2||Unknown||REACT_17786 (Reactome)|