Small molecule antagonism of oxysterol-induced Epstein-Barr virus induced gene 2 (EBI2) activation

Tau Benned-Jensen; Christian M Madsen; Kristine N Arfelt; Christian Smethurts; Andy Blanchard; Robert Jepras; Mette M Rosenkilde

doi:10.1016/j.fob.2013.02.003

Small molecule antagonism of oxysterol-induced Epstein-Barr virus induced gene 2 (EBI2) activation

Tau Benned-Jensen, Christian M Madsen, Kristine N Arfelt, Christian Smethurts, Andy Blanchard, Robert Jepras, Mette M Rosenkilde

Research output: Contribution to journal › Journal article › Research › peer-review

31 Citations (Scopus)

Abstract

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.

Original language	English
Journal	FEBS Open Bio
Volume	3
Pages (from-to)	156-60
Number of pages	5
DOIs	https://doi.org/10.1016/j.fob.2013.02.003
Publication status	Published - 2013

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10.1016/j.fob.2013.02.003

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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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abstract = "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.",

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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

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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.

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DO - 10.1016/j.fob.2013.02.003

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JO - FEBS Open Bio

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SN - 2211-5463

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