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HeLa ZIP kinase induces diphosphorylation of myosin II regulatory light chain and reorganization of actin filaments in nonmuscle cells

Oncogene volume 20, pages 8175–8183 (2001)Cite this article

Abstract

Dlk/ZIP kinase is a serine/threonine kinase highly homologous to DAP kinase. We have reported that HeLa ZIP kinase (hZIPK) phosphorylated the regulatory light chain of myosin II (MRLC) at both Ser19 and Thr18 in vitro. In this study, we demonstrate that hZIPK also induces the diphosphorylation of MRLC in nonmuscle cells. Peptide mapping revealed that transient transfection of hZIPK into HeLa cells caused diphosphorylation of MRLC. In contrast, transfection of the kinase inactive mutant of hZIPK did not induce any phosphorylation of MRLC. Using antibodies specific for mono- or diphosphorylated MRLC, we showed that diphosphorylated MRLC induced by the overexpression of hZIPK was concentrated in striking aggregates or bundles of actin filaments in HeLa cells, while monophosphorylated MRLC showed no prominent localization to these aggregates. Overexpression of hZIPK also induced dramatic changes in cell shape and disruption of nuclear morphology reminiscent of changes during apoptosis. These effects of hZIPK were suppressed by the coexpression of a mutant MRLC where both phosphorylation sites were replaced with alanine, indicating that the changes in actin organization were a consequence of MRLC diphosphorylation. These results suggested that hZIPK plays a role in regulating actin organization and cell morphology in non-muscles and at least part of its effects are mediated through the diphosphorylation of MRLC.

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References

  • Bresnick AR . 1999 Curr. Opin. Cell Biol. 11: 26–33

  • Cho SY, Klemke RL . 2000 J. Cell Biol. 149: 223–236

  • Cohen O, Feinstein E, Kimchi A . 1997 EMBO J. 16: 998–1008

  • Fishkind DJ, Wang YL . 1991 J. Cell Biol. 114: 967–975

  • Goeckeler ZM, Wysolmerski RB . 1995 Mol. Cell Biol. 130: 613–627

  • Hanks SK, Quinn AM . 1991 Methods Enzymol. 200: 38–62

  • Ikebe M . 1989 Biochemistry 28: 8750–8755

  • Ikebe M, Hartshorne DJ . 1985 J. Biol. Chem. 260: 10027–10031

  • Ikebe M, Hartshorne DJ, Elzinga M . 1986 J. Biol. Chem. 261: 36–39

  • Ikebe M, Hartshorne DJ, Elzinga M . 1987 J. Biol. Chem. 262: 9569–9573

  • Ikebe M, Koretz J, Hartshorne DJ . 1988 J. Biol. Chem. 263: 6432–6437

  • Inbal B, Cohen O, Polak-Charcon S, Kopolovic J, Vadai E, Eisenbach L, Kimchi A . 1997 Nature 390: 180–184

  • Kawai T, Matsumoto M, Takeda K, Sanjo H, Akira S . 1998 Mol. Cell. Biol. 18: 1642–1651

  • Kawano Y, Fukata Y, Oshiro N, Amano M, Nakamura T, Ito M, Matsumura F, Inagaki M, Kaibuchi K . 1999 J. Cell Biol. 147: 1023–1037

  • Kögel D, Bierbaum H, Preuss U, Scheidtmann KH . 1999 Oncogene 18: 7212–7218

  • Kögel D, Plottner O, Landberg G, Christian S, Scheidtmann KH . 1998 Oncogene 17: 2645–2654

  • Laemmli UK . 1970 Nature 227: 680–685

  • MacDonald JA, Borman MA, Muranyi A, Somlyo AV, Hartshorne DJ, Haystead TAJ . 2001 Proc. Natl. Acad. Sci. USA 98: 2419–2424

  • Matsumura F, Ono S, Yamakita Y, Totsukawa G, Yamashiro S . 1998 J. Cell Biol. 140: 119–129

  • Mills JC, Stone NL, Erhardt J, Pittman RN . 1998 J. Cell Biol. 140: 627–636

  • Murata-Hori M, Murai N, Komatsu S, Uji Y, Hosoya H . 1998 Biomed. Res. 19: 111–115

  • Murata-Hori M, Suizu F, Iwasaki T, Kijuchi A, Hosoya H . 1999 FEBS Lett. 451: 81–84

  • Niiro N, Ikebe M . 2001 J. Biol. Chem. 276: 29567–29574

  • Page G, Kogel D, Rangnekar V, Scheidtmann KH . 1999 Oncogene 18: 7265–7273

  • Petrache I, Verin AD, Crow MT, Birukova A, Liu F, Garcia JGN . 2001 Am. J. Physiol. Lung Cell Mol. Physiol. 280: L1168–L1178

  • Sebbagh M, Renvoize C, Hamelin J, Riche N, Bertoglio J, Breard J . 2001 Nature Cell Biol. 3: 346–352

  • Sellers JR, Adelstein RS . 1987 The Enzymes. Boyer PD and Krebs EG (ed.) Academic Press: New York 18: pp. 381–418

  • Sellers JR, Spudlich JA, Sheetz MP . 1985 J. Cell Biol. 101: 1897–1902

  • Somlyo AV, Bradshaw D, Ramos S, Murphy C, Myers CE, Somlyo AP . 2000 Biochem. Biophys. Res. Commun. 269: 652–659

  • Totsukawa G, Yamakita Y, Yamashiro S, Hartshorne DJ, Sasaki Y, Matsumura F . 2000 J. Cell. Biol. 150: 797–806

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Acknowledgements

We are grateful to Drs K Katoh (National Cardiovascular Center Research Institute) and K Fujiwara (University of Rochester) for providing anti-pan myosin antibody. We thank A Kikuchi (Hiroshima University) for preparation of MLCK. We also thank Dr Yu-Li Wang (University of Massachusetts) for critical reading of this manuscript. This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan to M Murata-Hori and H Hosoya and by the Hayashi Memorial Foundation for Female Natural Scientists to M Murata-Hori.

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  1. Maki Murata-Hori

    Present address: University of Massachusetts Medical School, Biotech Four, Suite 327, 377 Plantation Street, Worcester, MA 01605, Massachusetts, USA

Authors and Affiliations

  1. Department of Biological Science, Graduate School of Science, Hiroshima University, Higashi-Hiroshima, 739-8526, Hiroshima, Japan

    Maki Murata-Hori, Yasuaki Fukuta, Kozue Ueda, Takahiro Iwasaki & Hiroshi Hosoya

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Correspondence to Hiroshi Hosoya.

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Murata-Hori, M., Fukuta, Y., Ueda, K. et al. HeLa ZIP kinase induces diphosphorylation of myosin II regulatory light chain and reorganization of actin filaments in nonmuscle cells. Oncogene 20, 8175–8183 (2001). https://doi.org/10.1038/sj.onc.1205055

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