Analysis of the human gene encoding latent transforming growth factor-β-binding protein-2

Muhammad M. Bashir, Ming Da Han, William R. Abrams, Thomas Tucker, Rong Ine Ma, Mark Gibson, Tim Ritty, Robert Mecham, Joel Rosenbloom

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Transforming growth factor (TGF)-β is secreted as an inactive complex, which frequently contains a large molecular weight binding protein designated latent TGF-β-binding protein (LTBP). Recently, the LTBPs have been shown to be a gene family that contains three known members and exhibits a multidomain structure containing cysteine-rich motifs that are also found in the fibrillin gene family. The present work seeks to characterize the gene encoding LTBP-2 and to compare its features to that of the other LTBPs and to the fibrillins. Human fibroblast libraries were used to isolate cDNA encoding LTBP-2 which was then used to identify LTBP-2 transcripts and to isolate the corresponding LTBP-2 gene. The cloned cDNA encodes a 195 kDa protein containing 20 epidermal growth factor (EGF)-like repeats, three repeats containing eight cysteines, and one segment that appears to be a hybrid of the two. Single exons encode EGF repeats while the eight-cysteine repeats are encoded in two exons. Northern analysis identified two transcripts of 7.5 and 9.0 kb, with the presently analyzed cDNA probably corresponding to the 7.5 transcript. Phylogenetic sequence comparisons demonstrated that LTBP-3 is more similar to LTBP-1 than LTBP-2, while LTBP-2 shows the most similarity to the fibrillins. These analyses suggest that LTBP-1 diverged from LTBP-3, and that LTBP-2 diverged from LTBP-1. Within the fibrillin family, fibrillin-1 is nearest to the LTBPs. While the domain structure of LTBP-2 is similar to that of the other LTBPs, LTBP-2 possesses unique regions that make it the largest member of the LTBP family. LTBP-2 may have dual functions as a member of the TGF-β latent complex and as a structural component of microfibrils.

Original languageEnglish
Pages (from-to)531-542
Number of pages12
JournalInternational Journal of Biochemistry and Cell Biology
Volume28
Issue number5
DOIs
StatePublished - May 1996

Keywords

  • Elastic microfibrils
  • Epidermal growth factor-like repeats
  • Fibrillin
  • TGF-β binding proteins

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