ISOLATION OF A NOVEL LATENT TRANSFORMING GROWTH-FACTOR-BETA BINDING-PROTEIN GENE (LTBP-3)

This paper reports the molecular cloning of a novel gene in the mouse that shows structural similarities to the microfibril protein fibrilli n and to the latent trans forming growth factor-beta (TGF-beta) bindin g protein (LTBP), a component of the latent TGF-beta complex. The gene was initially isolated during a low stringency polymerase chain react ion screen of a NIH 3T3 cell cDNA library using primers that amplify a human fibrillin-1 epidermal growth factor-like repeat, Three lines of evidence suggest that the mouse gene is a third member of the LTBP ge ne family, which we designate LTBP-3. First, the deduced polypeptide, which consists of 15 epidermal growth factor-like repeats, 3 TGF bindi ng protein repeats, and 2 proline- and glycine-rich sequences, shows 3 8.4% identity with LTBP-1 but only 27% identity with fibrillin-1. Seco nd, the gene appears to be co-expressed in developing mouse tissues wi th TGF-beta. Third, immunoprecipitation studies using mouse preosteobl ast MC3T3-E1 cells and a specific anti-peptide polyclonal antiserum re veal that the mouse polypeptide forms a complex with the TGF-beta 1 pr ecursor. Finally, we note that the LTBP-3 gene was recently localized to a distinct genetic locus (Li, X., Yin, W., Perez-Jurado, L., Bonadi o, J., and Francke, U. (1995) Mamm. Genome 6, 42-45). Identification o f a third binding protein provides further insight into a mechanism by which latent TGF-beta complexes can be targeted to connective tissue matrices and cells.