Transglutaminase-2: a new endostatin partner in the extracellular matrix of endothelial cells.
Endostatin, a C-terminal fragment of collagen XVIII, binds to TG-2 (transglutaminase-2) in a cation-dependent manner. Recombinant human endostatin binds to TG-2 with an affinity in the nanomolar range (Kd=6.8 nM). Enzymatic assays indicated that, in contrast with other extracellular matrix proteins, endostatin is not a glutaminyl substrate of TG-2 and is not cross-linked to itself by the enzyme. Two arginine residues of endostatin, Arg27 and Arg139, are crucial for its binding to TG-2. They are also involved in the binding to heparin [Sasaki, Larsson, Kreuger, Salmivirta, Claesson-Welsh, Lindahl, Hohenester and Timpl (1999) EMBO J. 18, 6240-6248], and to alpha5beta1 and alphavbeta3 integrins [Faye, Moreau, Chautard, Jetne, Fukai, Ruggiero, Humphries, Olsen and Ricard-Blum (2009) J. Biol. Chem. 284, 22029-22040], suggesting that endostatin is not able to interact simultaneously with TG-2 and heparan sulfate, or with TG-2 and integrins. Inhibition experiments support the hypothesis that the GTP-binding site of TG-2 is a potential binding site for endostatin. Endostatin and TG-2 are co-localized in the extracellular matrix secreted by endothelial cells under hypoxia, which stimulates angiogenesis. This interaction, occurring in a cellular context, might participate in the concerted regulation of angiogenesis and tumorigenesis by the two proteins.
Institut de Biologie et Chimie des Protéines, UMR Centre National de la Recherche Scientifique, University Lyon, France.
Clément
C
Faye
Antonio
A
Inforzato
Marine
M
Bignon
Daniel J
DJ
Hartmann
Laurent
L
Muller
Lionel
L
Ballut
Bjorn R
BR
Olsen
Anthony J
AJ
Day
Sylvie
S
Ricard-Blum
D002478:Cells, Cultured; D043170:Collagen Type XVIII / Q000737:chemistry / Q000378:metabolism; D043169:Endostatins / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D011485:Protein Binding; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D017434:Protein Structure, Tertiary; D020349:Surface Plasmon Resonance; D011503:Transglutaminases / Q000378:metabolism*
D043170:Collagen Type XVIII; D043169:Endostatins; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins