Direct binding of hepatocyte growth factor and vascular endothelial growth factor to CD44v6.
Fiche publication
Date publication
juin 2015
Journal
Bioscience reports
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MELY Yves, Dr RICHERT Ludovic
Tous les auteurs :
Volz Y, Koschut D, Matzke-Ogi A, Dietz MS, Karathanasis C, Richert L, Wagner MG, Mély Y, Heilemann M, Niemann HH, Orian-Rousseau V
Lien Pubmed
Résumé
CD44v6, a member of the CD44 family of transmembrane glycoproteins is a co-receptor for two receptor tyrosine kinases (RTKs), Met and VEGFR-2 (vascular endothelial growth factor receptor 2). CD44v6 is not only required for the activation of these RTKs but also for signalling. In order to understand the role of CD44v6 in Met and VEGFR-2 activation and signalling we tested whether CD44v6 binds to their ligands, HGF (hepatocyte growth factor) and VEGF (vascular endothelial growth factor), respectively. FACS analysis and cellular ELISA showed binding of HGF and VEGF only to cells expressing CD44v6. Direct binding of CD44v6 to HGF and VEGF was demonstrated in pull-down assays and the binding affinities were determined using MicroScale Thermophoresis, fluorescence correlation spectroscopy and fluorescence anisotropy. The binding affinity of CD44v6 to HGF is in the micromolar range in contrast with the high-affinity binding measured in the case of VEGF and CD44v6, which is in the nanomolar range. These data reveal a heparan sulfate-independent direct binding of CD44v6 to the ligands of Met and VEGFR-2 and suggest different roles of CD44v6 for these RTKs.
Mots clés
Antigens, CD44, metabolism, Cell Line, Tumor, HEK293 Cells, Hepatocyte Growth Factor, metabolism, Human Umbilical Vein Endothelial Cells, Humans, Protein Binding, Proto-Oncogene Proteins c-met, metabolism, Vascular Endothelial Growth Factor A, metabolism, Vascular Endothelial Growth Factor Receptor-2, metabolism
Référence
Biosci. Rep.. 2015 Jun;35(4):