Complementary deoxyribonucleic acid cloning of a messenger ribonucleic acid encoding transforming growth factor beta...

Using a human transforming growth factor beta 1 (TGF beta) cDNA probe, we have detected an RNA species migrating at about 1.7 kilobases in cultured primary chicken embryo chondrocytes that is distinct from chicken TGF beta 1. The cloning and sequencing of cDNAs corresponding to this chondrocyte RNA demonstrate that it represents a new member of the TGF beta family, which we have named TGF beta 4. Unlike previously described TGF beta which are 390 to 414 amino acids long, the predicted precursor protein of TGF beta 4 is only 304 amino acids and does not appear to contain a signal peptide. Also unique to this new TGF beta is an insertion of two amino acids near the N-terminus of the processed peptide which would result in a 114 amino acid mature protein after cleavage from the precursor at a tetrabasic arg-arg-arg-arg site. The nine cysteine residues characteristic of all TGF beta are conserved. TGF beta 4 shows 82%, 64%, and 71% identity with the amino acid sequences of processed TGF beta 1, 2, and 3, respectively.