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

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

31 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	FEBS Open Bio
Vol/bind	3
Sider (fra-til)	156-60
Antal sider	5
DOI	https://doi.org/10.1016/j.fob.2013.02.003
Status	Udgivet - 2013

Adgang til dokumentet

10.1016/j.fob.2013.02.003

Citationsformater

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

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.",

author = "Tau Benned-Jensen and Madsen, {Christian M} and Arfelt, {Kristine N} and Christian Smethurts and Andy Blanchard and Robert Jepras and Rosenkilde, {Mette M}",

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doi = "10.1016/j.fob.2013.02.003",

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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

SN - 2211-5463

VL - 3

SP - 156

EP - 160

JO - FEBS Open Bio

JF - FEBS Open Bio

ER -