Transforming growth factors

Abstract

The term transforming growth factor (TGF) has been applied to peptides that have the ability to confer the transformed phenotype on untransformed fibroblastic indicator cells in vitro. Peptides representing two distinct classes of TGFs have been purified to homogeneity. Type alpha and type beta TGFs are distinguished both chemically by their unique amino acid sequences and biologically by their different activities on cells. Type alpha TGFs are single chain peptides of 50-53 amino acids cross-linked by three disulphide bonds. They have strong homology to epidermal growth factor with which they compete for receptor binding. Type beta TGFs have a homodimeric structure comprised of two chains of 112 amino acids, each containing nine cysteine residues; TGF beta binds to a unique cell surface receptor. Type alpha TGFs are usually mitogenic for fibroblasts, whereas type beta TGFs have bifunctional effects on cell growth and can either stimulate or inhibit growth of the same cells, depending on conditions. The interactions of type alpha and beta TGFs can be either synergistic or antagonistic. Though the development of peptide antagonists to type alpha TGFs may have therapeutic potential for the treatment of malignancy, type beta TGFs may inhibit tumorigenesis.