RRC ID 29146
著者 Fukamachi K, Matsuoka Y, Ohno H, Hamaguchi T, Tsuda H.
タイトル Neuronal leucine-rich repeat protein-3 amplifies MAPK activation by epidermal growth factor through a carboxyl-terminal region containing endocytosis motifs.
ジャーナル J Biol Chem
Abstract Neuronal leucine-rich repeat protein-3 (NLRR-3) belongs to the LRR superfamily. Expression of rat NLRR-3 gene isolated from c-Ha-ras transgenic rat tumor is regulated mainly through the Ras-MAPK signaling pathway. NLRR-3 was found to enhance phosphorylation of MAPK when COS-7 cells were transfected with NLRR-3 and stimulated with a low concentration (0.01 ng/ml) of epidermal growth factor (EGF), but the amplification of MAPK phosphorylation by NLRR-3 was no longer observed when the carboxyl-terminal 30 amino acid stretch containing clathrin-mediated endocytosis motifs was deleted. A green fluorescent protein-tagged NLRR-3 localized at the plasma membrane was efficiently internalized in COS-7 cells, but internalization of a carboxyl-terminal-deleted version (NLRRDeltaC) was less efficient. The presence of clathrin-adaptor protein complexes containing NLRR-3 in brain lysate was confirmed by immunoprecipitation and glutathione S-transferase pull-down experiments, and affinity column chromatography revealed that the carboxyl-terminal region of NLRR-3 interacts with beta-adaptin. We propose that NLRR-3 potentiates Ras-MAPK signaling by facilitating internalization of EGF in clathrin-coated vesicles.
巻・号 277(46)
ページ 43549-52
公開日 2002-11-15
DOI 10.1074/jbc.C200502200
PII S0021-9258(19)71686-X
PMID 12297494
MeSH 3T3 Cells Adaptor Protein Complex beta Subunits / metabolism Amino Acid Motifs Amino Acid Sequence Animals Blotting, Western Brain / metabolism COS Cells Endocytosis Enzyme Activation Epidermal Growth Factor / metabolism* Escherichia coli / metabolism Glutathione Transferase / metabolism Leucine / chemistry* MAP Kinase Signaling System* Membrane Glycoproteins Mice Microscopy, Fluorescence Models, Biological Molecular Sequence Data Nerve Tissue Proteins / metabolism Nerve Tissue Proteins / physiology* Phosphorylation Plasmids / metabolism Precipitin Tests Protein Binding Protein Structure, Tertiary Rats Recombinant Fusion Proteins / metabolism Sequence Homology, Amino Acid Time Factors Transfection
IF 4.238
引用数 34
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
遺伝子材料 pUSE-NLRR3 (RDB03437)