Synthesis of biologically active rat transforming growth factor I.

The hypothesis that some transformed cells produce endogenous transforming growth factors (TGFs) has been supported by isolation of peptide factors from transformed cells. One group of TGFs, TGF-I, produced only by transformed cells, displays sequence homology with the functionally related mouse submaxillary epidermal growth factor ( mEGF ). Both TGF-I and mEGF exhibit similar activities in competition for binding to the EGF receptor, stimulation of DNA synthesis and cell growth. Another group of TGFs, TGF-II (also known as TGF beta), present both in normal and transformed cells, is structurally and functionally unrelated to TGF-I or EGF, and does not compete for binding to the EGF receptor or induce cell growth. However, TGF-I or EGF in the presence of TGF-II produces a synergistic effect that is responsible for the observed phenotypic transformation of NRK fibroblasts. The complete amino acid sequence of rat TGF-I ( rTGF -I) from transformed Fischer rat embryo fibroblasts, has recently been determined. Using this proposed sequence, we have now prepared synthetic rTGF -I by the solid-phase synthesis method and find that it exhibits chemical and biological properties indistinguishable from those of natural rTGF -I. Since synthetic rTGF -I is free of any biological contaminants, our findings provide independent evidence that rTGF -I is an active principle in the transformation of cells.