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.
Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States.
Svetlana A
SA
Kuznetsova
David J
DJ
Mahoney
Gema
G
Martin-Manso
Tariq
T
Ali
Hilke A
HA
Nentwich
John M
JM
Sipes
Bixi
B
Zeng
Tikva
T
Vogel
Anthony J
AJ
Day
David D
DD
Roberts
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