First Author | Zadeh SM | Year | 1997 |
Journal | Endocrinology | Volume | 138 |
Issue | 7 | Pages | 3069-72 |
PubMed ID | 9202255 | Mgi Jnum | J:42022 |
Mgi Id | MGI:894952 | Doi | 10.1210/endo.138.7.5380 |
Citation | Zadeh SM, et al. (1997) The 16-kDa proteolytic fragment of insulin-like growth factor (IGF) binding protein-3 inhibits the mitogenic action of fibroblast growth factor on mouse fibroblasts with a targeted disruption of the type 1 IGF receptor gene. Endocrinology 138(7):3069-72 |
abstractText | We previously reported that a 16-kDa proteolytic fragment of IGF Binding Protein-3 (IGFBP-3), which is devoid of affinity for IGFs, inhibits the mitogenic effects of IGF-I on chick embryo fibroblasts. Here, we set out to determine if the fragment had biological effects on fibroblasts from mouse embryos homozygous for a targeted disruption of the Type 1 IGF receptor gene. In the cell clone used, bFGF (but not IGF, EGF or PDGF) was mitogenic in serum-free medium, increasing 14C-thymidine uptake by a factor of 10-15 within 24 hours and doubling cell proliferation. The 16-kDa fragment, isolated by HPLC following limited proteolysis of recombinant human (rh) IGFBP-3 by plasmin, in both assays dose-dependently (20 to 100 ng/ml) inhibited (up to 100%) maximal stimulation induced by 25 ng/ml bFGF, whereas intact IGFBP-3 had virtually no effect. Similar results were obtained with control wild-type cells. In the latter, the mitogenic activity of 1% fetal calf serum (equal to that of 25 ng/ml bFGF) was inhibited by only 25-30% by 100 ng/ml 16-kDa fragment or 200 ng/ml rhIGFBP-3. This agrees with an antagonistic action, affecting the mitogenic activity of serum that is attributable to IGFs. The 16-kDa IGFBP-3 fragment therefore appears to be a potent inhibitor of mitogenic signals resulting from activation of both the type 1 IGF and FGF receptors. |