論文 - 詳細
| RRC ID | 4265 |
|---|---|
| 著者 | Mizuno T, Fujiki K, Sasakawa A, Hisamoto N, Matsumoto K. |
| タイトル | Role of the Caenorhabditis elegans Shc adaptor protein in the c-Jun N-terminal kinase signaling pathway. |
| ジャーナル | Mol Cell Biol |
| Abstract |
Mitogen-activated protein kinases (MAPKs) are integral to the mechanisms by which cells respond to physiological stimuli and a wide variety of environmental stresses. In Caenorhabditis elegans, the stress response is controlled by a c-Jun N-terminal kinase (JNK)-like mitogen-activated protein kinase (MAPK) signaling pathway, which is regulated by MLK-1 MAPK kinase kinase (MAPKKK), MEK-1 MAPK kinase (MAPKK), and KGB-1 JNK-like MAPK. In this study, we identify the shc-1 gene, which encodes a C. elegans homolog of Shc, as a factor that specifically interacts with MEK-1. The shc-1 loss-of-function mutation is defective in activation of KGB-1, resulting in hypersensitivity to heavy metals. A specific tyrosine residue in the NPXY motif of MLK-1 creates a docking site for SHC-1 with the phosphotyrosine binding (PTB) domain. Introduction of a mutation that perturbs binding to the PTB domain or the NPXY motif abolishes the function of SHC-1 or MLK-1, respectively, thereby abolishing the resistance to heavy metal stress. These results suggest that SHC-1 acts as a scaffold to link MAPKKK to MAPKK activation in the KGB-1 MAPK signal transduction pathway. |
| 巻・号 | 28(23) |
| ページ | 7041-9 |
| 公開日 | 2008-12-1 |
| DOI | 10.1128/MCB.00938-08 |
| PII | MCB.00938-08 |
| PMID | 18809575 |
| PMC | PMC2593375 |
| MeSH | Adaptor Proteins, Signal Transducing Animals Binding Sites Caenorhabditis elegans Caenorhabditis elegans Proteins / metabolism* JNK Mitogen-Activated Protein Kinases / metabolism* MAP Kinase Kinase 1 / metabolism* Metals, Heavy / toxicity Mutation Shc Signaling Adaptor Proteins / physiology* Signal Transduction* Stress, Physiological |
| IF | 3.611 |
| 引用数 | 19 |
| 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
|
| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| 線虫 | tm1729 |