Direct evidence for an important role of sphingomyelinase in ultraviolet-induced activation of c-Jun N-terminal kinase

Chuanshu Huang, Wei Ya Ma, Min Ding, G. Tim Bowden, Zigang Dong

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

Sphingomyelinase (SMase) and its product ceramide have recently attracted a great deal of attention because of their possible role in the signal transduction pathway. However, the role of sphingomyelinase in UV- induced c-June N-terminal kinase (JNK) activation is still unclear. Thus, we investigated this issue directly using a genetic SMase-deficient (2 ~3% residual acid SMase activity) lymphoblast cell line, MS1418. The results showed that while UV irradiation markedly induces JNK activation in a normal human lymphoblast cell line, JY, it induces only weak JNK activation in MS1418 cells. This difference of JNK response to UV irradiation between these two cell lines was further observed in time course and dose-response studies. In contrast, 12-O-tetradecanoylphorbol-13-acetate-induced JNK activation could be observed in both JY and MS1418 cells. Furthermore, significant JNK activation can be observed in MS1418 cells by exposure of the cells to SMase or C2-ceramide, whereas phospholipase A2 or phospholipase C did not show significant induction of JNK activity, and C2-dihydroceramide and sphingosine induce only much weaker JNK activation in MS1418 cells than that by C2-ceramide. These data demonstrated that SMase plays an essential role in UV-induced JNK activation.

Original languageEnglish (US)
Pages (from-to)27753-27757
Number of pages5
JournalJournal of Biological Chemistry
Volume272
Issue number44
DOIs
StatePublished - Oct 31 1997

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