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) |