Insulin-like growth factors (IGFs) and IGF binding protein-3 display disulfide isomerase activity.
Insulin-like growth factors (IGF-I and -II) bind with high affinity to IGF-binding proteins (IGFBPs). IGFBP-3 contains vicinal cysteines in sequence which is similar to the active sites in thioredoxin and protein disulfide isomerase. We tested if, in analogy with these redox enzymes, IGFBP-3 could catalyze the isomerization of intramolecular disulfide bridges in protein substrates. IGFBP-3 (30 microM) was able to reactivate reduced ribonuclease at a rate of 38% of that of thioredoxin. Also recombinant IGF-I induced the regeneration of ribonuclease activity. Thiol redox reactions are known to play a role in regulating conformational changes in the insulin receptor and possibly also in the IGF-I receptor. Therefore, the intrinsic isomerase activities of IGF-I may be important in the activation of its receptor. The observed effects of IGFBP-3 may help to elucidate the mechanism by which this binding protein can modulate the actions of IGF-I.
Koedam
J A
JA
Department of Paediatrics, Wilhelmina Children's Hospital, Utrecht University, The Netherlands.
van den Brande
J L
JL
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002417:Cattle; D004789:Enzyme Activation; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000737:chemistry / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000737:chemistry / Q000378:metabolism*; D007535:Isomerases / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008969:Molecular Sequence Data; D010179:Pancreas / Q000201:enzymology; D019704:Protein Disulfide-Isomerases; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D013879:Thioredoxins / Q000737:chemistry / Q000378:metabolism
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D011994:Recombinant Proteins; D013879:Thioredoxins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D012259:Ribonuclease, Pancreatic; D007535:Isomerases; D019704:Protein Disulfide-Isomerases