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
リソース情報
線虫 tm1729