Interactions of recombinant and platelet transforming growth factor-β1 precursor with the insulin-like growth factor II/mannose 6-phosphate receptor

Abstract

Recombinant transforming growth factor (TGF)-β1 precursor was recently found to contain mannose 6-phosphate (Purchio et al., 1988, J. Biol. Chem. 263, 14211–14215). In the present study, recombinant TGF-β1 precursor was shown to bind to the insulin-like growth factor (IGF)-II/mannose 6-phosphate (man6P) receptor on the plasma membrane of cells since: 1) Insulin, which induces an increase in cell surface IGF-II/man6P receptors on adipocytes, caused a 2.7-fold increase in TGF-β1 precursor binding to adipocytes; 2) Chinese hamster ovary cells selected for overexpression of the IGF-II/man6P receptor exhibited an increased binding of TGF-β1 precursor in comparison to the parental cells; and 3) the binding of 125I-TGF-β1 precursor to these transfected cells and adipocytes was largely inhibited by man6P. After 15 minutes at 37°C, 75% of the recombinant TGF-β1 precursor was found to be internalized in the transfected cells. Additional studies with latent TGF-β1 isolated from platelets indicated that this material could also bind to the isolated IGF-II/man6P receptor.