The COOH terminus of Rho-kinase negatively regulates Rho-kinase activity

Mutsuki Amano, Kazuyasu Chihara, Nao Nakamura, Takako Kaneko, Yoshiharu Matsuura, Kozo Kaibuchi

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212 Citations (Scopus)

Abstract

Rho-kinase is implicated in the phosphorylation of myosin light chain downstream of Rho, which is thought to induce smooth muscle contraction and stress fiber formation in non-muscle cells. Here, we examined the mode of action of inhibitors of Rho-kinase. The chemical compounds such as HA1077 and Y-32885 inhibited not only the Rho-kinase activity but also the activity of protein kinase N, one of the targets of Rho, but had less of an effect on the activity of myotonic dystrophy kinase-related Cdc42-binding kinase β (MRCKβ). The COOH-terminal portion of Rho-kinase containing Rho-binding (RB) and pleckstrin homology (PH) domains (RB/PH (TT)), in which point mutations were introduced to abolish the Rho binding activity, interacted with Rho- kinase and thereby inhibited the Rho-kinase activity, whereas RB/PH (TT) had no effect on the activity of protein kinase N or MRCKβ, suggesting that the COOH-terminal region of Rho-kinase is a possible negative regulatory region of Rho-kinase. The expression of RB/PH (TT) specifically blocked the stress fiber and focal adhesion formation induced by the active form of Rho or Rho- kinase in NIH 3T3 cells, but not that induced by the active form of MRCKβ or myosin light chain. Thus, RB/PH (TT) appears to specifically inhibit Rho- kinase in vivo.

Original languageEnglish
Pages (from-to)32418-32424
Number of pages7
JournalJournal of Biological Chemistry
Volume274
Issue number45
DOIs
Publication statusPublished - 05-11-1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Amano, M., Chihara, K., Nakamura, N., Kaneko, T., Matsuura, Y., & Kaibuchi, K. (1999). The COOH terminus of Rho-kinase negatively regulates Rho-kinase activity. Journal of Biological Chemistry, 274(45), 32418-32424. https://doi.org/10.1074/jbc.274.45.32418