Structural and Sequence Analysis of TGF-β2 cDNA Clones Predicts Two Different Precursor Proteins Produced by Alternative mRNA Splicing

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Abstract
Analysis of cDNA clones coding for human and simian transforming growth factor-β2 (TGF-β2) revealed the existence of two types of TGF-β2 precursor proteins of 414 amino acids (TGF-β2,414) and 442 amino acids (TGF-β2,442) in length. TGF-β2,442 contains a 29-amino-acid insertion in the amino terminus of the precursor region that replaces an Asn residue located at position 116 in TGF-β2,414. Of these 29 amino acids, three are cysteines, suggesting a more extensive disulfide-bond mediated secondary structure for TGF-β2,442 than for TGF-β2,414. Northern blot analysis using probes specific for the insert in TGF-β2,442 indicated that this protein is encoded by a minor 5.1-kb mRNA species present in human and simian cells. Since the DNA sequences flanking the insert are identical between clones coding for the two precursor proteins, we suggest mRNAs coding for these proteins arise via differential splicing. Evidence is also presented that indicates that additional TGF-β2 mRNA heterogeneity is due to alternate polyadenylation. We propose that the 414-amino-acid precursor be referred to as TGF-β2a and the 442-amino-acid precursor be referred to as TGF-β2b.