Small molecule antagonism of oxysterol-induced Epstein-Barr virus induced gene 2 (EBI2) activation
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Small molecule antagonism of oxysterol-induced Epstein-Barr virus induced gene 2 (EBI2) activation. / Benned-Jensen, Tau; Madsen, Christian M; Arfelt, Kristine N; Smethurts, Christian; Blanchard, Andy; Jepras, Robert; Rosenkilde, Mette M.
In: FEBS Open Bio, Vol. 3, 2013, p. 156-60.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Small molecule antagonism of oxysterol-induced Epstein-Barr virus induced gene 2 (EBI2) activation
AU - Benned-Jensen, Tau
AU - Madsen, Christian M
AU - Arfelt, Kristine N
AU - Smethurts, Christian
AU - Blanchard, Andy
AU - Jepras, Robert
AU - Rosenkilde, Mette M
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
U2 - 10.1016/j.fob.2013.02.003
DO - 10.1016/j.fob.2013.02.003
M3 - Journal article
C2 - 23772388
VL - 3
SP - 156
EP - 160
JO - FEBS Open Bio
JF - FEBS Open Bio
SN - 2211-5463
ER -
ID: 48310696