Open AccessSmall molecule antagonism of oxysterol‐induced Epstein–Barr virus induced gene 2 (EBI2) activation
Author(s) -
Benned-Jensen Tau,
Madsen Christian M.,
Arfelt Kristine N.,
Smethurst Christian,
Blanchard Andy,
Jepras Robert,
Rosenkilde Mette M.
Publication year - 2013
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1016/j.fob.2013.02.003
Subject(s) - oxysterol , microbiology and biotechnology , antagonism , immune system , signalling , biology , phosphorylation , chemotaxis , kinase , effector , receptor , chemistry , biochemistry , immunology , cholesterol
The Epstein–Barr virus induced gene 2 (EBI2) was recently identified as the first oxysterol‐activated 7TM receptor. EBI2 is essential for B cell trafficking within lymphoid tissues and thus the humoral immune response in general. Here we characterize the antagonism of the non‐peptide molecule GSK682753A, which blocks oxysterol‐induced G‐protein activation, β‐arrestin recruitment and B‐cell chemotaxis. We furthermore demonstrate that activation triggers pertussis toxin‐sensitive MAP kinase phosphorylation, which is also inhibited by GSK682753A. Thus, EBI2 signalling in B cells mediates key phenotypic functions via signalling pathways amenable to manipulation providing additional therapeutic options for inhibiting EBI2 activity.