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.