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Science 2 February 1996:
Vol. 271. no. 5249, pp. 648 - 650
DOI: 10.1126/science.271.5249.648
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Reports

Identification of a Putative Target for Rho as the Serine-Threonine Kinase Protein Kinase N

Mutsuki Amano,  Hideyuki Mukai,  Yoshitaka Ono,  Kazuyasu Chihara,  Takeshi Matsui,  Yuko Hamajima,  Katsuya Okawa,  Akihiro Iwamatsu,  Kozo Kaibuchi (1)

Rho, a Ras-like small guanosine triphosphatase, has been implicated in cytoskeletal responses to extracellular signals such as lysophosphatidic acid (LPA) to form stress fibers and focal contacts. The form of RhoA bound to guanosine triphosphate directly bound to and activated a serine-threonine kinase, protein kinase N (PKN). Activated RhoA formed a complex with PKN and activated it in COS-7 cells. PKN was phosphorylated in Swiss 3T3 cells stimulated with LPA, and this phosphorylation was blocked by treatment of cells with botulinum C3 exoenzyme. Activation of Rho may be linked directly to a serine-threonine kinase pathway.


M. Amano, K. Chihara, T. Matsui, Y. Hamajima, K. Kaibuchi, Division of Signal Transduction, Nara Institute of Science and Technology, Ikoma 630-01, Japan.
H. Mukai and Y. Ono, Department of Biology, Faculty of Science, Kobe University, Kobe 657, Japan.
K. Okawa and A. Iwamatsu, Central Laboratories for Key Technology, Kirin Brewery Company Limited, Yokohama 236, Japan.
(1) To whom correspondence should be addressed.


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S. Gasman, S. Chasserot-Golaz, P. Hubert, D. Aunis, and M.-F. Bader (1998)
J. Biol. Chem. 273, 16913-16920
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Physiological Features of Visceral Smooth Muscle Cells, With Special Reference to Receptors and Ion Channels.
H. KURIYAMA, K. KITAMURA, T. ITOH, and R. INOUE (1998)
Physiol Rev 78, 811-920
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Signal Transduction and Signal Modulation by Cell Adhesion Receptors: The Role of Integrins, Cadherins, Immunoglobulin-Cell Adhesion Molecules, and Selectins.
A. E. Aplin, A. Howe, S. K. Alahari, and R. L. Juliano (1998)
Pharmacol. Rev. 50, 197-264
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Inhibition of Rho Is Required for cAMP-induced Melanoma Cell Differentiation.
R. Buscà, C. Bertolotto, P. Abbe, W. Englaro, T. Ishizaki, S. Narumiya, P. Boquet, J.-P. Ortonne, and R. Ballotti (1998)
Mol. Biol. Cell 9, 1367-1378
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Phosphatidic Acid-induced Elevation of Intracellular Ca2+ Is Mediated by RhoA and H2O2 in Rat-2 Fibroblasts.
Z.-W. Lee, S.-M. Kweon, B.-C. Kim, S.-H. Leem, I. Shin, J.-H. Kim, and K.-S. Ha (1998)
J. Biol. Chem. 273, 12710-12715
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Phosphorylation of Vimentin by Rho-associated Kinase at a Unique Amino-terminal Site That Is Specifically Phosphorylated during Cytokinesis.
H. Goto, H. Kosako, K. Tanabe, M. Yanagida, M. Sakurai, M. Amano, K. Kaibuchi, and M. Inagaki (1998)
J. Biol. Chem. 273, 11728-11736
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Requirement for Rho-mediated Myosin Light Chain Phosphorylation in Thrombin-stimulated Cell Rounding and Its Dissociation from Mitogenesis.
M. Majumdar, T. M. Seasholtz, D. Goldstein, P. de Lanerolle, and J. H. Brown (1998)
J. Biol. Chem. 273, 10099-10106
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Association of the Myosin-binding Subunit of Myosin Phosphatase and Moesin: Dual Regulation of Moesin Phosphorylation by Rho-associated Kinase and Myosin Phosphatase.
Y. Fukata, K. Kimura, N. Oshiro, H. Saya, Y. Matsuura, and K. Kaibuchi (1998)
J. Cell Biol. 141, 409-418
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Crystal Structure of Human RhoA in a Dominantly Active Form Complexed with a GTP Analogue.
K. Ihara, S. Muraguchi, M. Kato, T. Shimizu, M. Shirakawa, S. Kuroda, K. Kaibuchi, and T. Hakoshima (1998)
J. Biol. Chem. 273, 9656-9666
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Analysis of RhoA-binding Proteins Reveals an Interaction Domain Conserved in Heterotrimeric G Protein beta  Subunits and the Yeast Response Regulator Protein Skn7.
A. S. Alberts, N. Bouquin, L. H. Johnston, and R. Treisman (1998)
J. Biol. Chem. 273, 8616-8622
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Rho Guanosine Triphosphatase Mediates the Selective Stabilization of Microtubules Induced by Lysophosphatidic Acid.
T. A. Cook, T. Nagasaki, and G. G. Gundersen (1998)
J. Cell Biol. 141, 175-185
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Comparative Effects of GTPgamma S and Insulin on the Activation of Rho, Phosphatidylinositol 3-Kinase, and Protein Kinase N in Rat Adipocytes. RELATIONSHIP TO GLUCOSE TRANSPORT.
M. Standaert, G. Bandyopadhyay, L. Galloway, Y. Ono, H. Mukai, and R. Farese (1998)
J. Biol. Chem. 273, 7470-7477
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The Low Molecular Weight GTPase Rho Regulates Myofibril Formation and Organization in Neonatal Rat Ventricular Myocytes. INVOLVEMENT OF Rho KINASE.
M. Hoshijima, V. P. Sah, Y. Wang, K. R. Chien, and J. H. Brown (1998)
J. Biol. Chem. 273, 7725-7730
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Regulation of the Association of Adducin with Actin Filaments by Rho-associated Kinase (Rho-kinase) and Myosin Phosphatase.
K. Kimura, Y. Fukata, Y. Matsuoka, V. Bennett, Y. Matsuura, K. Okawa, A. Iwamatsu, and K. Kaibuchi (1998)
J. Biol. Chem. 273, 5542-5548
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The Rho Family G Proteins Play a Critical Role in Muscle Differentiation.
H. Takano, I. Komuro, T. Oka, I. Shiojima, Y. Hiroi, T. Mizuno, and Y. Yazaki (1998)
Mol. Cell. Biol. 18, 1580-1589
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