HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 277, Issue 46, 43549-43552, November 15, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/46/43549    most recent C200502200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fukamachi, K. Articles by Tsuda, H. Search for Related Content PubMed PubMed Citation Articles by Fukamachi, K. Articles by Tsuda, H.

ACCELERATED PUBLICATION
Neuronal Leucine-rich Repeat Protein-3 Amplifies MAPK Activation by Epidermal Growth Factor through a Carboxyl-terminal Region Containing Endocytosis Motifs^*

Katsumi Fukamachi^§, Yoichiro Matsuoka^¶, Hiroshi Ohno^**, Tetsuya Hamaguchi^§, and Hiroyuki Tsuda^¶

From the  Experimental Pathology, Chemotherapy Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, the  Division of Molecular Membrane Biology, Cancer Research Institute, Kanazawa University, Kanazawa 920-0934, Japan, and the ^** RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, Japan

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 (NLRRC) 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 -adaptin. We propose that NLRR-3 potentiates Ras-MAPK signaling by facilitating internalization of EGF in clathrin-coated vesicles.

This article has been cited by other articles:

				T. Bando, K. Sekine, S. Kobayashi, A. M. Watabe, A. Rump, M. Tanaka, Y. Suda, S. Kato, Y. Morikawa, T. Manabe, et al. Neuronal Leucine-Rich Repeat Protein 4 Functions in Hippocampus-Dependent Long-Lasting Memory Mol. Cell. Biol., May 15, 2005; 25(10): 4166 - 4175. [Abstract] [Full Text] [PDF]