De novo synthesis of sphingolipids is required for cell survival by down-regulating c-Jun N-terminal kinase in <i>Drosophila</i> imaginal discs

作     者：Adachi-Yamada, T Gotoh, T Sugimura, I Tateno, M Nishida, Y Onuki, T Date, H 

作者机构：Nagoya Univ Grad Sch Sci Div Biol Sci Chikusa Ku Nagoya Aichi 4648602 Japan 

出 版 物：《MOLECULAR AND CELLULAR BIOLOGY》 (分子生物学与细胞生物学)

年 卷 期：1999年第19卷第10期

页      面：7276-7286页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 07[理学] 

主　　题：酰基转移酶类/遗传学 酰基转移酶类/代谢 氨基酸序列 动物 基因修饰 细胞存活 克隆 分子 交叉 遗传 DNA 互补/遗传学 减量调节 果蝇属/胚胎学 眼/胚胎学 头部/胚胎学 JNK丝裂原活化蛋白激酶类 膜蛋白质类/遗传学 膜蛋白质类/代谢 丝裂原激活蛋白激酶类/代谢 模型 生物学 分子序列数据 突变 蛋白质加工 转译后 序列分析 DNA 序列同源性 氨基酸 丝氨酸C-棕榈酰转移酶 鞘脂类/生物合成 动物 女(雌)性 男(雄)性 

摘      要：Mitogen-activated protein kinase (MAPK) is a conserved eukaryotic signaling factor that mediates various signals, cumulating in the activation of transcription factors. Extracellular signal-regulated kinase (ERK), a MAPK? is activated through phosphorylation by the kinase MAP/ERK kinase (MEK). To elucidate the extent of the involvement of ERR in various aspects of animal development, we searched for a Drosophila mutant which responds to elevated MEK activity and herein identified a lace mutant. Mutants with mild lace alleles grow to become adults with multiple aberrant morphologies in the appendages, compound eye, and bristles. These aberrations were suppressed by elevated MEK activity. Structural and transgenic analyses of the lace cDNA have revealed that the lace gene product is a membrane protein similar to the yeast protein LCB2, a subunit of serine palmitoyltransferase (SPT), which catalyzes the first step of sphingolipid biosynthesis. In fact, SPT activity in the fly expressing epitope-tagged Lace was absorbed by epitope-specific antibody. The number of dead cells in various imaginal discs of a lace hypomorph was considerably increased, thereby ectopically activating c-Jun N-terminal kinase (JNK), another MAPK These results account for the adult phenotypes of the lace mutant and suppression of the phenotypes by elevated MEK activity we hypothesize that mutation of lace causes decreased de novo synthesis of sphingolipid metabolites, some of which are signaling molecules, and one or more of these changes activates JNK to elicit apoptosis, The ERK pathway may be antagonistic to the JNK pathway in the control of cell survival.