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

Journal article

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.

Authors: Kuznetsova, SA; Mahoney, D; Martin-Manso, G; Ali, T; Nentwich, H

• Publication status: Published
• Journal: Matrix biology : journal of the International Society for Matrix Biology
• Volume: 27
• Issue: 3
• Pages: 201-210
• Publication date: 2008-04-01
• DOI: 10.1016/j.matbio.2007.10.003
• EISSN: 1569-1802
• ISSN: 0945-053X
• Language: English
• Keywords: Cell Adhesion Molecules; Thrombospondin 1; Fibroblasts; Protein Structure, Tertiary; Fibronectins; Kinetics; Models, Biological; Humans; Integrin alpha5beta1; Recombinant Proteins; Gene Deletion; Cations; Dose-Response Relationship, Drug; Extracellular Matrix; Ligands