論文 - 詳細
| RRC ID | 30431 |
|---|---|
| 著者 | Adachi-Yamada T, Gotoh T, Sugimura I, Tateno M, Nishida Y, Onuki T, Date H. |
| タイトル | De novo synthesis of sphingolipids is required for cell survival by down-regulating c-Jun N-terminal kinase in Drosophila imaginal discs. |
| ジャーナル | Mol Cell Biol |
| Abstract |
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 MAPK/ERK kinase (MEK). To elucidate the extent of the involvement of ERK 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. |
| 巻・号 | 19(10) |
| ページ | 7276-86 |
| 公開日 | 1999-10-1 |
| DOI | 10.1128/MCB.19.10.7276 |
| PMID | 10490662 |
| PMC | PMC84720 |
| MeSH | Acyltransferases / genetics Acyltransferases / metabolism* Amino Acid Sequence Animals Animals, Genetically Modified Cell Survival Cloning, Molecular Crosses, Genetic DNA, Complementary / genetics Down-Regulation Drosophila / embryology* Eye / embryology Female Head / embryology JNK Mitogen-Activated Protein Kinases Male Membrane Proteins / genetics Membrane Proteins / metabolism Mitogen-Activated Protein Kinases / metabolism* Models, Biological Molecular Sequence Data Mutation Protein Processing, Post-Translational* Sequence Analysis, DNA Sequence Homology, Amino Acid Serine C-Palmitoyltransferase Sphingolipids / biosynthesis* Wings, Animal / embryology |
| IF | 3.611 |
| 引用数 | 81 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ショウジョウバエ | DGRC#109638 |