The small GTP-binding protein Rho binds to and activates a 160 kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase

Toshimasa Ishizaki, Midori Maekawa, Kazuko Fujisawa, Katsuya Okawa, Akihiro Iwamatsu, Akiko Fujita, Naoki Watanabe, Yuji Saito, Akira Kakizuka, Narito Morii, Shuh Narumiya

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    744 Citations (Scopus)

    Abstract

    The small GTP-binding protein Rho functions as a molecular switch in the formation of focal adhesions and stress fibers, cytokinesis and transcriptional activation. The biochemical mechanism underlying these actions remains unknown. Using a ligand overlay assay, we purified a 160 kDa platelet protein that bound specifically to GTP-bound Rho. This protein, p160, underwent autophosphorylation at its serine and threonine residues and showed the kinase activity to exogenous substrates. Both activities were enhanced by the addition of GTP-bound Rho. A cDNA encoding p160 coded for a 1354 amino acid protein. This protein has a Ser/Thr kinase domain in its N-terminus, followed by a coiled-coil structure ~600 amino acids long, and a cysteine-rich zinc finger-like motif and a pleckstrin homology region in the C-terminus. The N-terminus region including a kinase domain and a part of coiled-coil structure showed strong homology to myotonic dystrophy kinase over 500 residues. When co-expressed with RhoA in COS cells, p160 was co-precipitated with the expressed Rho and its kinase activity was activated, indicating that p160 can associate physically and functionally with Rho both in vitro and in vivo.

    Original languageEnglish
    Pages (from-to)1885-1893
    Number of pages9
    JournalEMBO Journal
    Volume15
    Issue number8
    DOIs
    Publication statusPublished - 1996 Apr 15

    Keywords

    • Coiled-coil structure
    • Myotonic dystrophy kinase
    • Protein kinase
    • Rho
    • Small GTP-binding protein

    ASJC Scopus subject areas

    • Neuroscience(all)
    • Molecular Biology
    • Biochemistry, Genetics and Molecular Biology(all)
    • Immunology and Microbiology(all)

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  • Cite this

    Ishizaki, T., Maekawa, M., Fujisawa, K., Okawa, K., Iwamatsu, A., Fujita, A., Watanabe, N., Saito, Y., Kakizuka, A., Morii, N., & Narumiya, S. (1996). The small GTP-binding protein Rho binds to and activates a 160 kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase. EMBO Journal, 15(8), 1885-1893. https://doi.org/10.1002/j.1460-2075.1996.tb00539.x