TSG-6 binds via its CUB_C domain to the cell-binding domain of fibronectin and increases fibronectin matrix assembly.
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.
Kuznetsova
Svetlana A
SA
Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States.
Mahoney
David J
DJ
Martin-Manso
Gema
G
Ali
Tariq
T
Nentwich
Hilke A
HA
Sipes
John M
JM
Zeng
Bixi
B
Vogel
Tikva
T
Day
Anthony J
AJ
Roberts
David D
DD
D002412:Cations; D015815:Cell Adhesion Molecules / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005353:Fibronectins / Q000737:chemistry* / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D008954:Models, Biological; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D019700:Thrombospondin 1 / Q000737:chemistry / Q000378:metabolism
D002412:Cations; D015815:Cell Adhesion Molecules; D005353:Fibronectins; D039081:Integrin alpha5beta1; D008024:Ligands; D011994:Recombinant Proteins; C072273:TNFAIP6 protein, human; D019700:Thrombospondin 1