Cleavage of sphingosine kinase 2 by caspase-1 provokes its release from apoptotic cells.
Cleavage of sphingosine kinase 2 by caspase-1 provokes its release from apoptotic cells.
复制标题
DOI：
10.1182/blood-2009-10-243444
复制
发表时间：
2010-04
期刊：
影响因子：
20.3
通讯作者：
A. Weigert;S. Cremer;Martina Schmidt;A. von Knethen;C. Angioni;G. Geisslinger;B. Brüne
中科院分区：
文献类型：
--
作者：
A. Weigert;S. Cremer;Martina Schmidt;A. von Knethen;C. Angioni;G. Geisslinger;B. Brüne
被称为凋亡的生理性细胞死亡的执行受到严格调控，并传递免疫相关信息。这确保了对死亡细胞的有效清除，并塑造了它们的“捕获者”的抗炎表型。在这里，我们确定了凋亡细胞产生鞘氨醇-1-磷酸的机制。在细胞死亡过程中，鞘氨酸激酶2 （SphK2）在其n端以caspase-1依赖性的方式被切割。因此，SphK2的一个截断但具有酶活性的片段从细胞中释放出来。这一步骤与磷脂酰丝氨酸暴露相结合，磷脂酰丝氨酸暴露是细胞凋亡的标志，也是吞噬细胞/凋亡细胞相互作用的关键信号。我们的数据将细胞凋亡过程中的信号事件与影响免疫细胞吸引和激活的脂质介质的细胞外生产联系起来。
Execution of physiologic cell death known as apoptosis is tightly regulated and transfers immunologically relevant information. This ensures efficient clearance of dying cells and shapes the phenotype of their "captors" toward anti-inflammatory. Here, we identify a mechanism of sphingosine-1-phosphate production by apoptotic cells. During cell death, sphingosine kinase 2 (SphK2) is cleaved at its N-terminus in a caspase-1-dependent manner. Thereupon, a truncated but enzymatically active fragment of SphK2 is released from cells. This step is coupled to phosphatidylserine exposure, which is a hallmark of apoptosis and a crucial signal for phagocyte/apoptotic cell interaction. Our data link signaling events during apoptosis to the extracellular production of a lipid mediator that affects immune cell attraction and activation.