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

被引：30

作者：

Benned-Jensen, Tau ^{[1
]}

Madsen, Christian M. ^{[1
]}

Arfelt, Kristine N. ^{[1
]}

Smethurst, Christian ^{[2
]}

Blanchard, Andy ^{[2
]}

Jepras, Robert ^{[2
]}

Rosenkilde, Mette M. ^{[1
]}

机构：

[1] Univ Copenhagen, Fac Hlth & Med Sci, Dept Neurosci & Pharmacol, Mol Pharmacol Lab, DK-2200 Copenhagen N, Denmark

[2] GlaxoSmithKline, Stevenage SG1 2NY, Herts, England

来源：

FEBS OPEN BIO | 2013年 / 3卷

关键词：

7TM receptors; EB12; Oxysterols; Antagonism; MAP kinase activation; Epstein-Barr virus; 7-TRANSMEMBRANE RECEPTOR; STRUCTURAL MOTIFS; CELL-MIGRATION; IDENTIFICATION; BINDING; BILF1;

D O I：

10.1016/j.fob.2013.02.003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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, beta-arrest in 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. (C) 2013 The Authors. Published by Elsevier B.V. on behalf of Federation of European Biochemical Societies. All rights reserved,

引用

页码：156 / 160

页数：5

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