Efficient synthesis of human type α transforming growth factor: Its physical and biological characterization

Human transforming growth factor type α (TGF-α) was synthesized by a stepwise solid-phase method with an overall yield of 26%. Synthetic TGF-α, consisting of 50 amino acid residues deduced from a cDNA precursor sequence, was purified in a single HPLC step. The homogeneity and primary structure were confirmed by several criteria including Edman degradation and mass spectrometry. Synthetic TGF-α was as active as murine epidermal growth factor in binding to the epidermal growth factor receptor and in stimulation of anchorage-dependent and of anchorage-independent growth of normal indicator cells in culture. Synthetic TGF-α stimulated plasminogen activator production in A 431 and HeLa cells; the stimulation was similar to that induced by epidermal growth factor. Furthermore, synthetic human TGF-α showed similar immunoreactivity when compared with rat TGF-α. Thus, the 50-amino acid TGF-α is likely to be the bioactive principle produced and secreted by tumor cell lines.