Phosphorylation of ERM proteins at filopodia induced by Cdc42

Nao Nakamura, Noriko Oshiro, Yuko Fukata, Mutsuki Amano, Masaki Fukata, Shinya Kuroda, Yoshiharu Matsuura, Thomas Leung, Louis Lim, Kozo Kaibuchi

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96 Citations (Scopus)

Abstract

Background: ERM (ezrin, radixin, and moesin) proteins function as membrane-cytoskeletal linkers, and are known to be localized at filopodia and microvilli-like structures. We have shown that Rho-associated kinase (Rho- kinase)/ROKα/ROCK II phosphorylates moesin at Thr-558 at the lower stream of Rho, and the phosphorylation is crucial to the formation of microvilli-like structures (Oshiro, N., Fukata, Y. and Kaibuchi, K. (1998) Phosphorylation of moesin by Rho-associated kinase (Rho-kinase) plays a crucial role in the formation of microvilli-like structures. J. Biol. Chem. 273, 34663-34666). However, the role of ERM proteins in the formation of filopodia is less well characterized. Results: Here we examined the phosphorylation state of ERM during filopodia formation induced by Cdc42 using the antibody recognizing ERM proteins phosphorylated at COOH (C)-terminal threonine. When NIH 3T3 cells were transfected with constitutively active Cdc42 (Cdc42(V12)), filopodia formation was induced and phosphorylation of ERM at C-terminal threonine was observed at the tip of filopodia, while the phosphorylation levels of ERM were lower and phosphorylated ERM was distributed throughout the cytoplasm in the control cells. We also showed that Myotonic dystrophy kinase-related Cdc42-binding kinase (MACK) which has been identified as an effector of Cdc42, phosphorylated moesin at C-terminal threonine in a cell- free system. Coexpression of the dominant negative form of MaCK inhibited both the formation of filopodia and accumulation of C-terminal threonine- phosphorylated ERM proteins at filopodin induced by Cdc42(V12). Conclusion: The formation of filopodia induced by Cdc42 is accompanied by phosphorylation of ERM proteins, and MaCK is a candidate for the kinase that phosphorylates ERM proteins at filopodia.

Original languageEnglish
Pages (from-to)571-581
Number of pages11
JournalGenes to Cells
Volume5
Issue number7
DOIs
Publication statusPublished - 2000

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cell Biology

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