TSG-6 binds via its CUB_C domain to the cell-binding domain of fibronectin and increases fibronectin matrix assembly

Matrix Biol. 2008 Apr;27(3):201-10. doi: 10.1016/j.matbio.2007.10.003. Epub 2007 Oct 25.

Abstract

Human plasma fibronectin binds with high affinity to the inflammation-induced secreted protein TSG-6. Fibronectin binds to the CUB_C domain of TSG-6 but not to its Link module. TSG-6 can thus act as a bridging molecule to facilitate fibronectin association with the TSG-6 Link module ligand thrombospondin-1. Fibronectin binding to TSG-6 is divalent cation-independent and is conserved in cellular fibronectins. Based on competition binding studies using recombinant and proteolytic fragments of fibronectin, TSG-6 binding localizes to type III repeats 9-14 of fibronectin. This region of fibronectin contains the Arg-Gly-Asp sequence recognized by alpha5beta1 integrin, but deletion of that sequence does not prevent TSG-6 binding, and TSG-6 does not inhibit cell adhesion on fibronectin substrates mediated by this integrin. This region of fibronectin is also involved in fibronectin matrix assembly, and addition of TSG-6 enhances exogenous and endogenous fibronectin matrix assembly by human fibroblasts. Therefore, TSG-6 is a high affinity ligand that can mediate fibronectin interactions with other matrix components and modulate some interactions of fibronectin with cells.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cations
  • Cell Adhesion Molecules / chemistry*
  • Dose-Response Relationship, Drug
  • Extracellular Matrix / metabolism*
  • Fibroblasts / metabolism
  • Fibronectins / chemistry*
  • Fibronectins / metabolism
  • Gene Deletion
  • Humans
  • Integrin alpha5beta1 / metabolism
  • Kinetics
  • Ligands
  • Models, Biological
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Thrombospondin 1 / chemistry
  • Thrombospondin 1 / metabolism

Substances

  • Cations
  • Cell Adhesion Molecules
  • Fibronectins
  • Integrin alpha5beta1
  • Ligands
  • Recombinant Proteins
  • TNFAIP6 protein, human
  • Thrombospondin 1