鞘氨醇激酶1
鞘氨醇激酶
鞘氨醇
组蛋白脱乙酰基酶
脂质信号
孤儿受体
促炎细胞因子
自身免疫性疾病
激酶
生物
免疫学
癌症研究
炎症
细胞生物学
受体
组蛋白
1-磷酸鞘氨醇
生物化学
转录因子
抗体
基因
作者
Nigel J. Pyne,David R. Adams,Susan Pyne
标识
DOI:10.1016/j.tips.2017.04.003
摘要
The purpose of this Opinion is to present a case for targeting sphingosine kinase 2 (SK2) in autoimmune/inflammatory disease. Data obtained using Sphk2-/- mice suggest that SK2 is an anti-inflammatory enzyme, although this might be misleading because of a compensatory increase in the expression of a second isoform, sphingosine kinase 1 (SK1), which functions as a proinflammatory enzyme. SK2 is involved in regulating interleukin (IL)-12/interferon gamma (IFN-γ) and histone deacetylase-1/2 (HDAC-1/2) signalling and, potentially, retinoid-related orphan receptor gamma t (ROR-γt) stability linked with T helper (Th) 17 cell polarisation. Therefore, there is a need to develop highly potent SK2 inhibitors with selectivity over SK1 to clearly define the role of SK2 in autoimmune/inflammatory disease. Structural determinants of SK2 relative to SK1 will enable the design of selective SK2 inhibitors.
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