Isolation of a novel latent transforming growth factor-β binding protein gene (LTBP-3)

W. Yin, E. Smiley, J. Germiller, R. P. Mecham, J. B. Florer, R. J. Wenstrup, J. Bonadio

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Abstract

This paper reports the molecular cloning of a novel gene in the mouse that shows structural similarities to the microfibril protein fibrillin and to the latent transforming growth factor-β (TGF-β) binding protein (LTBP), a component of the latent TGF-β complex. The gene was initially isolated during a low stringency polymerase chain reaction 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 gene family, which we designate LTBP-3. First, the deduced polypeptide, which consists of 15 epidermal growth factor-like repeats, 3 TGF binding protein repeats, and 2 proline- and glycine-rich sequences, shows 38.4% identity with LTBP-1 but only 27% identity with fibrillin-1. Second, the gene appears to be co-expressed in developing mouse tissues with TGF-β. Third, immunoprecipitation studies using mouse preosteoblast MC3T3-E1 cells and a specific anti-peptide polyclonal antiserum reveal that the mouse polypeptide forms a complex with the TGF-β1 precursor. Finally, we note that the LTBP-3 gene was recently localized to a distinct genetic locus (Li, X., Yin, W., Perez-Jurado, L., Bonadio, J. and Francke, U. (1995) Mamm. Genome 6, 42-45). Identification of a third binding protein provides further insight into a mechanism by which latent TGF-β complexes can be targeted to connective tissue matrices and cells.

Original languageEnglish
Pages (from-to)10147-10160
Number of pages14
JournalJournal of Biological Chemistry
Volume270
Issue number17
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

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    Yin, W., Smiley, E., Germiller, J., Mecham, R. P., Florer, J. B., Wenstrup, R. J., & Bonadio, J. (1995). Isolation of a novel latent transforming growth factor-β binding protein gene (LTBP-3). Journal of Biological Chemistry, 270(17), 10147-10160. https://doi.org/10.1074/jbc.270.17.10147