Molecular mechanism of environmental stress-induced apoptosis in fish

中性鞘磷脂酶1(NSMase1)参与了环境应激诱导的细胞凋亡。为了揭示其分子机制，我们研究了应激激活蛋白激酶/c-jun氨基末端激酶(SAPK/JNK)系统的变化。在热休克处理后，蛋白激酶启动了一条导致细胞死亡(细胞凋亡)的信号转导途径。利用重组JNK1蛋白，我们发现nSMase1的磷酸化发生在丝氨酸-270处。热休克处理能迅速提高内源JNK的nSMase1导向的激酶活性。另一方面，JNK1显性负性突变体对热休克的敏感性要低得多。我们的结果有力地表明，热休克诱导的细胞凋亡中nSMase1的磷酸化是由JNK执行的。

The neutral sphingomyelinase １ (nSMase1) is involved in environmental stress-i duced apoptosis infish. To reveal the molecular mechanism, we examined the invo vement of the stress-activated protein kinase/c-jun N-terminal kinase (SAPK/JNK) system. Upon heat shock treatment, the protein kinase initiated a signal transduction pathway leading to cell death (apoptosis). Using recombinant JNK1 protein, we found that phosphorylation of nSMase1 occurred at serine-270. Treatment with heat shock rapidly enhanced the nSMase1-directed kinase activity of endogenous JNK. On the other hand, the mutant of JNK1 dominant negative was much less sensitve to heat shock. Our results strongly suggest that phosphorylation of nSMase1 in heat-shock-induced apoptosis is executed by JNK.