Transglutaminase-2: A new endostatin partner in the extracellular matrix of endothelial cells

Clément Faye, Antonio Inforzato, Marine Bignon, Daniel J. Hartmann, Laurent Muller, Lionel Ballut, Bjorn R. Olsen, Anthony J. Day, Sylvie Ricard-Blum

Research output: Contribution to journalArticle

Abstract

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 α5β1 and αvβ3 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.

Original languageEnglish
Pages (from-to)467-475
Number of pages9
JournalBiochemical Journal
Volume427
Issue number3
DOIs
Publication statusPublished - May 1 2010

Keywords

  • Endostatin (ES)
  • Extracellular matrix
  • Protein-protein interaction
  • Surface plasmon resonance (SPR) binding assays
  • Transglutaminase-2 (TG-2)

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Fingerprint Dive into the research topics of 'Transglutaminase-2: A new endostatin partner in the extracellular matrix of endothelial cells'. Together they form a unique fingerprint.

  • Cite this

    Faye, C., Inforzato, A., Bignon, M., Hartmann, D. J., Muller, L., Ballut, L., Olsen, B. R., Day, A. J., & Ricard-Blum, S. (2010). Transglutaminase-2: A new endostatin partner in the extracellular matrix of endothelial cells. Biochemical Journal, 427(3), 467-475. https://doi.org/10.1042/BJ20091594