Fibronectin is required for integrin αvβ6-mediated activation of latent TGF-β complexes containing LTBP-1

Laura Fontana, Yan Chen, Petra Prijatelj, Takao Sakai, Reinhard Fässler, Lynn Sakai, Daniel B. Rifkin

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

Transforming growth factor-βs (TGF-β) are secreted as latent complexes consisting of the TGF-β dimer, the TGF-β propeptide dimer, and the latent TGF-β binding protein (LTBP). Although the bonds between TGF-β and its propeptide are cleaved intracellulary, the propeptide associates with TGF-β by electrostatic interactions, thereby conferring latency to the complex. We reported that a specific sequence of LTBP-1 is required for latent TGF-β activation by the integrin αvβ6. Here we describe a 24 amino acid sequence from the hinge domain required for activation. The LTBP-1 polypeptide rL1N, which includes the hinge, associates with fibronectin in binding assays. We present evidence that fibronectin null cells minimally activate latent TGF-β and poorly incorporate the active hinge sequence into their matrix. In addition, cells missing the fibronectin receptor α5β1 exhibit defective activation of latent TGF-β by αvβ6 and decreased matrix incorporation. The results indicate specificity for integrin-mediated latent TGF-β activation that include unique sequences in LTBP-1 and an appropriate matrix molecule.

Original languageEnglish (US)
Pages (from-to)1798-1808
Number of pages11
JournalFASEB Journal
Volume19
Issue number13
DOIs
StatePublished - Nov 1 2005

Fingerprint

Transforming Growth Factors
Fibronectins
Integrins
Carrier Proteins
Chemical activation
Hinges
Dimers
Integrin alpha5beta1
Null Lymphocytes
Coulomb interactions
Static Electricity
Amino Acid Sequence
Assays
Amino Acids
Peptides
Molecules

Keywords

  • Fibronectin null cells
  • LTBP
  • TGF-β

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Fibronectin is required for integrin αvβ6-mediated activation of latent TGF-β complexes containing LTBP-1. / Fontana, Laura; Chen, Yan; Prijatelj, Petra; Sakai, Takao; Fässler, Reinhard; Sakai, Lynn; Rifkin, Daniel B.

In: FASEB Journal, Vol. 19, No. 13, 01.11.2005, p. 1798-1808.

Research output: Contribution to journalArticle

Fontana, L, Chen, Y, Prijatelj, P, Sakai, T, Fässler, R, Sakai, L & Rifkin, DB 2005, 'Fibronectin is required for integrin αvβ6-mediated activation of latent TGF-β complexes containing LTBP-1', FASEB Journal, vol. 19, no. 13, pp. 1798-1808. https://doi.org/10.1096/fj.05-4134com
Fontana, Laura ; Chen, Yan ; Prijatelj, Petra ; Sakai, Takao ; Fässler, Reinhard ; Sakai, Lynn ; Rifkin, Daniel B. / Fibronectin is required for integrin αvβ6-mediated activation of latent TGF-β complexes containing LTBP-1. In: FASEB Journal. 2005 ; Vol. 19, No. 13. pp. 1798-1808.
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