The type V transforming growth factor beta receptor is the putative insulin-like growth factor-binding protein 3 receptor

Insulin-like growth factor-binding protein 3 (IGFBP-3) has been shown to inhibit cell growth by IGF-dependent and -independent mechanisms, The putative cell-surface IGFBP-3 receptor that mediates the IGF-independent growth inhibition has not been identified, Here we show that recombinant human IGFBP-3 inhibits I-125-transforming growth factor (TGF)-beta(1) binding to the type V TGF-beta receptor (M-r 400,000) in mink lung epithelial cells, We also demonstrate that the similar to 400-kDa I-125-IGFBP-3 affinity-labeled putative IGFBP-3 receptor is immunoprecipitated by specific antiserum to the type V TGF-beta receptor, The I-125-IGFBP-3 affinity labeling of the putative receptor and IGFBP-3-induced growth inhibition as measured by DNA synthesis in these cells is blocked by a TGF-beta(1) peptide antagonist, The I-125-IGFBP-3 affinity-labeled putative receptor can only be detected in cells expressing the type V TGF-beta receptor, but not in cells lacking the type V TGF-beta receptor, These results indicate that the type V TGF-beta receptor is the putative IGFBP-3 receptor and that IGFBP-3 is a functional ligand for the type V TGF-beta receptor.