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 Sakai

Research output: Contribution to journalArticle

368 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Microfibrils
Transforming Growth Factors
Carrier Proteins
Tissue
Proteins
Extracellular Matrix
Macromolecules
Binding Sites
Cells
Cytokines
Fibrillins
Connective Tissue
Cultured Cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Latent transforming growth factor β-binding protein 1 interacts with fibrillin and is a microfibril-associated protein. / Isogai, Zenzo; Ono, Robert N.; Ushiro, Shin; Keene, Douglas R.; Chen, Yan; Mazzieri, Roberta; Charbonneau, Noe L.; Reinhardt, Dieter P.; Rifkin, Daniel B.; Sakai, Lynn.

In: Journal of Biological Chemistry, Vol. 278, No. 4, 24.01.2003, p. 2750-2757.

Research output: Contribution to journalArticle

Isogai, Z, Ono, RN, Ushiro, S, Keene, DR, Chen, Y, Mazzieri, R, Charbonneau, NL, Reinhardt, DP, Rifkin, DB & Sakai, L 2003, 'Latent transforming growth factor β-binding protein 1 interacts with fibrillin and is a microfibril-associated protein', Journal of Biological Chemistry, vol. 278, no. 4, pp. 2750-2757. https://doi.org/10.1074/jbc.M209256200
Isogai, Zenzo ; Ono, Robert N. ; Ushiro, Shin ; Keene, Douglas R. ; Chen, Yan ; Mazzieri, Roberta ; Charbonneau, Noe L. ; Reinhardt, Dieter P. ; Rifkin, Daniel B. ; Sakai, Lynn. / Latent transforming growth factor β-binding protein 1 interacts with fibrillin and is a microfibril-associated protein. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 4. pp. 2750-2757.
@article{963e8f7972914fb5b449d8d41b135da6,
title = "Latent transforming growth factor β-binding protein 1 interacts with fibrillin and is a microfibril-associated protein",
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.",
author = "Zenzo Isogai and Ono, {Robert N.} and Shin Ushiro and Keene, {Douglas R.} and Yan Chen and Roberta Mazzieri and Charbonneau, {Noe L.} and Reinhardt, {Dieter P.} and Rifkin, {Daniel B.} and Lynn Sakai",
year = "2003",
month = "1",
day = "24",
doi = "10.1074/jbc.M209256200",
language = "English (US)",
volume = "278",
pages = "2750--2757",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "4",

}

TY - JOUR

T1 - Latent transforming growth factor β-binding protein 1 interacts with fibrillin and is a microfibril-associated protein

AU - Isogai, Zenzo

AU - Ono, Robert N.

AU - Ushiro, Shin

AU - Keene, Douglas R.

AU - Chen, Yan

AU - Mazzieri, Roberta

AU - Charbonneau, Noe L.

AU - Reinhardt, Dieter P.

AU - Rifkin, Daniel B.

AU - Sakai, Lynn

PY - 2003/1/24

Y1 - 2003/1/24

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0037462678&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037462678&partnerID=8YFLogxK

U2 - 10.1074/jbc.M209256200

DO - 10.1074/jbc.M209256200

M3 - Article

C2 - 12429738

AN - SCOPUS:0037462678

VL - 278

SP - 2750

EP - 2757

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 4

ER -