Isolation and characterization of proteolytic fragments of insulin-like growth factor-binding protein-3.
Limited proteolysis of insulin-like growth factor-binding protein-3 (IGFBP-3) is a normal process in the regulation of insulin-like growth factor (IGF) activity, which we have reproduced in vitro using plasmin and recombinant human non-glycosylated IGFBP-3 in order to isolate and characterize the fragments obtained. Two major fragments of 22-25 and 16 kD were purified by RP-HPLC. The 22- to 25-kD fragment had severely reduced affinity for IGF-I, compared with intact IGFBP-3. It weakly inhibited cell proliferation stimulated by IGF-I and had no effect on insulin-induced stimulation. The 16-kD fragment, which had lost all affinity for IGFs, unexpectedly proved to be a potent inhibitor of both IGF-I-induced and insulin-induced cell growth. This proteolytic fragment of IGFBP-3 therefore exhibits intrinsic inhibitory activity.
Lalou
C
C
Institut National de la Santé et de la Recherche Médicale, Unité 142, Hôpital Saint-Antoine, Paris, France.
Lassarre
C
C
Binoux
M
M
D000818:Animals; D001667:Binding, Competitive; D002417:Cattle / Q000097:blood; D002642:Chick Embryo; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000302:isolation & purification* / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D010446:Peptide Fragments / Q000302:isolation & purification* / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000302:isolation & purification* / Q000378:metabolism*; D011994:Recombinant Proteins
D018972:Insulin-Like Growth Factor Binding Protein 3; D010446:Peptide Fragments; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D010447:Peptide Hydrolases