Latent transforming growth factor β-binding protein 1 interacts with fibrillin and is a microfibril-associated protein

Zenzo Isogai, Robert N. Ono, Shin Ushiro, Douglas R. Keene, Yan Chen, Roberta Mazzieri, Noe L. Charbonneau, Dieter P. Reinhardt, Daniel B. Rifkin, Lynn Y. Sakai

Research output: Contribution to journalArticle

384 Scopus citations

Abstract

Latent transforming growth factor β-binding protein I (LTBP-1) targets latent complexes of transforming growth factor β to the extracellular matrix, where the latent cytokine is subsequently activated by several dif-ferent mechanisms. Fibrillins are extracellular matrix macromolecules whose primary function is architectur-al: fibrillins assemble into ultrastructurally distinct mi-crofibrils that are ubiquitous in the connective tissue space. LTBPs and fibrillins are highly homologous mol-ecules, and colocalization in the matrix of cultured cells has been reported. To address whether LTBP-1 func-tions architecturally like fibrillins, microfibrils were ex-tracted from tissues and analyzed immunochemically. In addition, binding studies were conducted to deter-mine whether LTBP-1 interacts with fibrillins. LTBP-1 was not detected in extracted beaded-string microfi-brils, suggesting that LTBP-1 is not an integral struc-tural component of microfibrils. However, binding studies demonstrated interactions between LTBP-1 and fibrillins. The binding site was within three domains of the LTBP-1 C terminus, and in fibrillin-1 the site was defined within four domains near the N terminus. Immunolocalization data were consistent with the hypothesis that LTBP-1 is a fibrillin-associated protein present in certain tissues but not in others. In tissues where LTBP-1 is not expressed, LTBP-4 may substitute for LTBP-1, because the C-terminal end of LTBP-4 binds equally well to fibrillin. A model depicting the relationship between LTBP-1 and fibrillin microfibrils is proposed.

Original languageEnglish (US)
Pages (from-to)2750-2757
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number4
DOIs
StatePublished - Jan 24 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Isogai, Z., Ono, R. N., Ushiro, S., Keene, D. R., Chen, Y., Mazzieri, R., Charbonneau, N. L., Reinhardt, D. P., Rifkin, D. B., & Sakai, L. Y. (2003). Latent transforming growth factor β-binding protein 1 interacts with fibrillin and is a microfibril-associated protein. Journal of Biological Chemistry, 278(4), 2750-2757. https://doi.org/10.1074/jbc.M209256200