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, Shinya Tanaka

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Abstract

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.

Original languageEnglish
Pages (from-to)46843-46850
Number of pages8
JournalJournal of Biological Chemistry
Volume279
Issue number45
DOIs
Publication statusPublished - 2004 Nov 5

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Tsuda, M., Makino, Y., Iwahara, T., Nishihara, H., Sawa, H., Nagashima, K., Hanafusa, H., & Tanaka, S. (2004). Crk associates with ERM proteins and promotes cell motility toward hyaluronic acid. Journal of Biological Chemistry, 279(45), 46843-46850. https://doi.org/10.1074/jbc.M401476200