title: A proteolytic fragment of insulin-like growth factor (IGF) binding protein-3 that fails to bind IGF is a cell growth inhibitor.
abstract: Limited proteolysis of insulin-like growth factor binding protein-3 (IGFBP-3) is now recognized as a normal process in the regulation of insulin-like growth factor (IGF) activity, its major effect being to increase IGF bioavialability. In order to characterize the proteolytic fragments of IGFBP-3, we reproduced this proteolysis in vitro using plasmin which provokes cleavages that are similar to those induced in vivo by (unidentified) specific IGFBP-3 proteases. Two major peaks were purified by RP-HPLC. One contained a 16 kDa fragment and the other comprised two fragments of 22 and 25 kDa. Competitive binding experiments showed that the 16 kDa material had no affinity for IGFs. The 22-25 kDa fragments had considerably reduced affinity, particularly for IGF-I. In a chick embryo fibroblast assay where DNA synthesis was stimulated by IGF-I or insulin, the 22-25 kDa fragments weakly inhibited IGF-I-induced cell proliferation and had no effect on stimulation by insulin. The 16 kDa fragment unexpectedly proved to be a potent inhibitor of both IGF- and insulin-induced cell growth. This proteolytic fragment of IGFBP-3 therefore exhibits intrinsic inhibitory activity.
authors.affiliation: Unité de Recherches sur la Régulation de la Croissance, Institut National de la Santé et de la Recherche Médicale U. 142, Hôpital Saint Antoine, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Lalou
authors.forename: C
authors.initials: C
authors.lastname: Lassarre
authors.forename: M
authors.initials: M
authors.lastname: Binoux
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002642:Chick Embryo; D005341:Fibrinolysin / Q000378:metabolism; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D008954:Models, Biological; D013002:Somatomedins / Q000378:metabolism*
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D013002:Somatomedins; D005341:Fibrinolysin