UV-C light induces raft-associated acid sphingomyelinase and JNK activation and translocation independently on a nuclear signal

被引:108
作者
Charruyer, A
Grazide, S
Bezombes, C
Müller, S
Laurent, G
Jaffrezou, JP [1 ]
机构
[1] CHU Purpan, Ctr Physiopathol Toulouse Purpan, INSERM, U563, F-31024 Toulouse, France
[2] CHU Purpan, Hematol Serv, F-31059 Toulouse, France
关键词
D O I
10.1074/jbc.M412867200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The initiation of UV light-induced signaling in mammalian cells is largely considered to be subsequent to DNA damage. Several studies have also described ceramide (CER), a lipid second messenger, as a major contributor in mediating UV light-induced c-Jun N-terminal kinase (JNK) activation and cell death. It is demonstrated here that UV-C light irradiation of U937 cells results in the activation and translocation of a Zn2+-independent acid sphingomyelinase, leading to CER accumulation in raft microdomains. These CER-enriched rafts aggregate and play a functional role in JNK activation. The observation that UV-C light also induced CER generation and the externalization of acid sphingomyelinase and JNK in human platelets conclusively rules out the involvement of a nuclear signal generated by DNA damage in the initiation of a UV light response, which is generated at the plasma membrane.
引用
收藏
页码:19196 / 19204
页数:9
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