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

J. Biol. Chem., Vol. 279, Issue 45, 46843-46850, November 5, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/45/46843    most recent M401476200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tsuda, M. Articles by Tanaka, S. Search for Related Content PubMed PubMed Citation Articles by Tsuda, M. Articles by Tanaka, S. Social Bookmarking                      What's this?

Crk Associates with ERM Proteins and Promotes Cell Motility toward Hyaluronic Acid^*

Masumi Tsuda, Yoshinori Makino, Toshinori Iwahara¶, Hiroshi Nishihara, Hirofumi Sawa, Kazuo Nagashima, Hidesaburo Hanafusa¶, and Shinya Tanaka||

From the Laboratory of Molecular and Cellular Pathology, Hokkaido University School of Medicine, N15, W7, Kita-ku, Sapporo 060-8638, ^¶Osaka Bioscience Institute, Suita 565-0874, Osaka, and CREST, Japan Science and Technology Corporation, Kawaguchi, Saitama 332-0012, Japan

Cell migration is a well organized process regulated by the extracellular matrix-mediated cytoskeletal reorganization. The signaling adaptor protein Crk has been shown to regulate cell motility, but its precise role is still under investigation. Herein, we report that Crk associates with ERM family proteins (including ezrin, radixin, and moesin), activates RhoA, and promotes cell motility toward hyaluronic acid. The binding of Crk with ERMs was demonstrated both by transient and stable protein expression systems in 293T cells and 3Y1 cells, and it was shown that v-Crk translocated the phosphorylated form of ERMs to microvilli in 3Y1 cells by immunofluorescence and immunoelectron microscopy. This v-Crk-dependent formation of microvilli was suppressed by inhibitors of Rho-associated kinase, and the activity of RhoA was elevated by coexpression of c-Crk-II and ERMs in 3Y1 cells. In concert with the activation of RhoA by Crk, Crk was found to associate with Rho-GDI, which has been shown to bind to ERMs. Furthermore, upon hyaluronic acid treatment, coexpression of c-Crk-II and ERMs enhanced cell motility, whereas the sole expression of c-Crk-II or either of the ERMs decreased the motility of 3Y1 cells. These results suggest that Crk may be involved in regulation of cell motility by a hyaluronic acid-dependent mechanism through an association with ERMs.

Received for publication, February 10, 2004 , and in revised form, July 26, 2004.

^* This work was supported in part by a grant from the Ministry of Education, Science, Culture, and Sports of Japan. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| To whom correspondence should be addressed. Tel.: 81-11-706-7806; Fax: 81-11-706-7806; E-mail: tanaka{at}med.hokudai.ac.jp.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K. Tabu, Y. Ohba, T. Suzuki, Y. Makino, T. Kimura, A. Ohnishi, M. Sakai, T. Watanabe, S. Tanaka, and H. Sawa Oligodendrocyte Lineage Transcription Factor 2 Inhibits the Motility of a Human Glial Tumor Cell Line by Activating RhoA Mol. Cancer Res., October 1, 2007; 5(10): 1099 - 1109. [Abstract] [Full Text] [PDF]

				M. Koss, G. R. Pfeiffer II, Y. Wang, S. T. Thomas, M. Yerukhimovich, W. A. Gaarde, C. M. Doerschuk, and Q. Wang Ezrin/Radixin/Moesin Proteins Are Phosphorylated by TNF-{alpha} and Modulate Permeability Increases in Human Pulmonary Microvascular Endothelial Cells J. Immunol., January 15, 2006; 176(2): 1218 - 1227. [Abstract] [Full Text] [PDF]

				S. Barker, M. Weinfeld, J. Zheng, L. Li, and D. Murray Identification of Mammalian Proteins Cross-linked to DNA by Ionizing Radiation J. Biol. Chem., October 7, 2005; 280(40): 33826 - 33838. [Abstract] [Full Text] [PDF]