The Type V Transforming Growth Factor β 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 inhibits125I-transforming growth factor (TGF)-β1 binding to the type V TGF-β receptor (M r 400,000) in mink lung epithelial cells. We also demonstrate that the ∼400-kDa125I-IGFBP-3 affinity-labeled putative IGFBP-3 receptor is immunoprecipitated by specific antiserum to the type V TGF-β receptor. The 125I-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-β1peptide antagonist. The 125I-IGFBP-3 affinity-labeled putative receptor can only be detected in cells expressing the type V TGF-β receptor, but not in cells lacking the type V TGF-β receptor. These results indicate that the type V TGF-β receptor is the putative IGFBP-3 receptor and that IGFBP-3 is a functional ligand for the type V TGF-β receptor.