| 1.Research Institution | Yokoahama City University | |
| 2.Research Area | Life Science | |
| 3.Research Field | Cellular Signaling | |
| 4.Term of Project | FY1996〜FY2000 | |
| 5.Project Number | 96L00305 | |
| 6.Title of Project | Regulation of Protein Kinases in Signal Transduction |
| Name | Institution,Department | Title of Position |
| Shigeo Ohno | Yokohama City University School of Medicine | Professor |
8.Core Members
| Names | Institution,Department | Title of Position |
| Syu-ichi Hirai | Yokohama City University School of Medicine | Associated Professor |
| Atsushi Suzuki | Yokohama City University School of Medicine | Lecturer |
| Keiko Mizuno | Yokohama City University School of Medicine | Assistant Professor |
9.Cooperating Researchers
| Names | Institution,Department | Title of Position |
| Tetsuo Ohnishi | Yokohama City University School of Medicine | Research Fellow |
| Yuki Sugiyama | Yokohama City University School of Medicine | Research Fellow |
| Masa-aki Nakaya | Yokohama City University School of Medicine | Research Fellow |
10.Summary of Research Results
|
We focused several protein kinases that include protein kinaseC(PKC) delta and lambda, mixed lineage kinases, and DMPK, and analyzed their regulatory mechanism through identification of their binding proteins. We found a novel member of the small heat shock protein family, MKBP, as a DMPK-specific binding protein. DMPK binds and stabilized DMPK, implying the role of DMPK as one of the components of a muscle-specific regulatory system that protoects muscle fibers from heat stress. As for PKC, we found and identified ASIP, atypical PKC-specific interacting protein, as a physiological binding partner of atypical PKJKC isotypes. ASIP is a PDZ domain-containing adaptor-like protein and is the mammalian orthologue of C. elegans PAR-3 and Drosophila Bazooka, both of which are involved in the establishment of cell polarity. ASIP as well as aPKC localize to the tight junctions of vertebrate epithelial cells and are required for the establishment of epithelial cell polarith that include the development of epithelia-specific junctional structures. We also found a novel member of the phosphatidylinositol kinase-related protein kinase (PIKK) family. This kinase was termed as hSMG-1 based on its close similarity to C. elegans SMG-1, one of the 7 smg genes involved in nonsense-mediated mRNA decay (NMD). In fact, we have succeeded in provide evidence supporting that hSMG-1 is involved in mammian NMD through phosphorylation of another component of the NMD system, hUpf1/SMG-2. |
11.Key Words
(1)PKC、(2)DMPK、(3)small HSP
(4)stress response、(5)polarity、(6)epithela
(7)PAR、(8)aPKC、(9)cell-cell junctions
12.References
| Author | Title of Article | |||
| Takaki, Y., Hirai, S., Manabe, N., Izumi, Y., Hirose, T., Nakaya, M., Suzuki, A., Mizuno, K., Akimoto, K., Shuin, T., and Ohno, S. | Dynamic changes in protein components of the tight junction during liver regeneration | |||
| Journal | Volume | Year | Pages Concerned | |
| Cell & Tissue Research | in press | |||
| Author | Title of Article | |||
| Baba, M., Hirai, S., Kawakami, S., Kishida, T., Sakai, N., Kaneko, S., Yao, M., Shuin, T., Hosaka, M., and Ohno, S. | Tumor suppressor protein VHL is induced at high cell density and mediates contact inhibition of cell growth. | |||
| Journal | Volume | Year | Pages Concerned | |
| Oncogene | in press | |||
| Author | Title of Article | |||
| Noda, Y., Takeya, R., Ohno, S., Naito, S., Ito, T., and Sumimoto, H. | Human homologues ofo the Caenorhabditis elegans cell polarity protein PAR6 as an adaptor that links the small GTPases Rac and Cdc42 to atypical protein kinase C. | |||
| Journal | Volume | Year | Pages Concerned | |
| Genes to Cells | 6 | 2001 | 107-119 | |
| Author | Title of Article | |||
| Suzuki, A., Yamanaka, T., Hashiba, K., Hirose, T., Izumi, Y., Ohnishi, T. and Ohno, S. | Atypical PKC is involved in the establishment of epithelial polarity in mammalian cells. | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Cell Biol. | 152 | 2001 | 1183-1196 | |
| Author | Title of Article | |||
| Nakaya, M., Fukui, A., Izumi, Y., Akimoto, K., Asashima, M., and Ohno, S. | Meiotic Maturation Induces Animal-Vegetal Asymmetric Distribution of aPKC and ASIP/PAR-3 in Xenopus oocytes. | |||
| Journal | Volume | Year | Pages Concerned | |
| Development | 127 | 2000 | 5021-5031 | |
| Author | Title of Article | |||
| Kotani K, Ogawa W, Hashiramoto M, Onishi T, Ohno S., Kasuga M. | Inhibition of insulin-induced glucose uptake by atypical protein kinase C isotype-specific interacting protein in 3T3-L1 adipocytes. | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Biol. Chem. | 275 | 2000 | 26390-26395 | |
| Author | Title of Article | |||
| Fukuyama, K., Yoshida, M., Yamashita, A., Deyama. T., Baba, M., Suzuki, A., Mohri, H., Ikezawa. Z., Nakajima. H., Hirai, S-I. and Ohno, S. | MAPK upstream kinase(MUK)-binding inhibitory protein, a negative regulator of MUK/dual leucine zipper-bearing kinase/leucine zipper protein kinase. | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Biol. Chem. | 275 | 2000 | 21247-21254 | |
| Author | Title of Article | |||
| Sugiyama, Y., Suzuki, A., Kishikawa, M., Akutsu, R., Hirose, T., Waye, M. M. Y., Tsui, S. K. W., Yoshida, S. and Ohno, S. | Muscle develops a specific form of small heat shock protein complex composed of MKBP/HSPB2 and HSPB3 during myogenic differentiation. | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Biol. Chem. | 275 | 2000 | 1095-1104 | |
| Author | Title of Article | |||
| Zhuang, S., Hisai, S. and Ohno, S. | Hyperosmolality induces activation of cPKC and nPKC, a requirement for ERK1/2 activation in NIH/3T3 cells. | |||
| Journal | Volume | Year | Pages Concerned | |
| Am. J. Physiol. Cell Physiol. | 278 | 2000 | 102-109 | |
| Author | Title of Article | |||
| Okuda, H., Hirai, S., Takaki, Y., Kamata, M., Baba, M., Sakai, N., Kishida, T., Kaneko, S., Yao, M., Ohno, S. and Shuin, T. | Direct interaction of the b-domain of VHL tumor suppressor protein with the regulatory domain of atypical PKC isotypes. | |||
| Journal | Volume | Year | Pages Concerned | |
| Biochem. Biophys. Res. Commun. | 263 | 1999 | 491-497 | |
| Author | Title of Article | |||
| Koike, H., Tomioka, S., Sorimachi, H., Saido, T. C., Maruyama, K., Okuyama, A., Fujisawa-Sehara, A., Ohno, S., Suzuki, K. and Ishiura, S. | MDC9 has an alpha-secretase activity responsible for processing the amyloid precursor protein. | |||
| Journal | Volume | Year | Pages Concerned | |
| Biochem. J. | 343 | 1999 | 371-375 | |
| Author | Title of Article | |||
| Imafuku, I., Masaki, T., Waragai, M., Takeuchi, S., Kawabata, M., Hirai, S., Ohno, S., Nee, L. E., Lippa, C. F., Kanazawa, I., Imagawa, M. and Okazawa, H. | Presenilin 1 Suppresses the function of c-Jun homodimers via interaction with QM/Jif-1. | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Cell Biol. | 147 | 1999 | 121-133 | |
| Author | Title of Article | |||
| Desai, D. S., Hirai, S., Kames, W. E. Jr., Niles, R. M. and Ohno, S. | Cloning and characterization of the murine PKCa promoter: identification of a retinoic acid response element. | |||
| Journal | Volume | Year | Pages Concerned | |
| Biochem. Biophys. Res. Commun. | 263 | 1999 | 25-34 | |
| Author | Title of Article | |||
| Miranti, C. K., Ohno, S. and Brugge, J. S. | Protein kinase C regulates integrin-induced activation of the extracellular regulated kinase pathway upstream of Shc. | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Biol. Chem. | 274 | 1999 | 10571-10581 | |
| Author | Title of Article | |||
| Izumi, Y., Hirata, M., Hasuwa, H., Iwamoto, R., Umata, T., Miyado, K., Tamai, Y., Kurisaki, T., Sehara-Fujisawa, A., Ohno, S. and Mekada, E. | A metalloprotease-disintegrin, MDC9/Meltrin-g/ADAM9, and PKCd are involved in TPA-induced ectodomain shedding of membrane-anchored heparin-binding EGF-like growth factor. | |||
| Journal | Volume | Year | Pages Concerned | |
| EMBO J . | 24 | 1998 | 7260-7272 | |
| Author | Title of Article | |||
| Kotani, K., Ogawa, W., Matsumoto, M., Kitamura, T., Sakaue, H., Hino, Y., Miyake, K., Sano, W., Akimoto, K., Ohno, S. and Kasuga M.: | Requirement of atypical PKC1 for insulin stimulation of glucose uptake but not for Akt activation in 3T3-L1 adipocytes. | |||
| Journal | Volume | Year | Pages Concerned | |
| Molecular and Cellular Biol. | 18 | 1998 | 6971-6982 | |
| Author | Title of Article | |||
| Izumi, Y., Hirose, T., Tamai, Y., Hirai, S-I., Nagashima, Y., Fujimoto, T., Tabuse, Y., Kemphues, K. J. and Ohno, S. | An atypical PKC directly associates and co-localizes at the epithelial tight junction with ASIP, a mammalian homologue of Caenorhabditis elegans polarity protein PAR-3. | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Cell Biol. | 143 | 1998 | 95-106 | |
| Author | Title of Article | |||
| Akimoto, K., Nakaya, M., Yamanaka, T., Tanaka, J., Matsuda, S., Weng, Q-P., Avruch, J. and Ohno, S. | Atypical PKC1 binds and regulates p70 S6 kinase. | |||
| Journal | Volume | Year | Pages Concerned | |
| Biochem. J. | 335 | 1998 | 417-424 | |
| Author | Title of Article | |||
| Tabuse, Y., Izumi, Y., Piano, F., Kemphues, K. J., Miwa, J. and Ohno, S. | Atypical Protein Kinase C Cooperates with PAR-3 to Establish Embryonic Polarity in Caenorhabditis elegans. | |||
| Journal | Volume | Year | Pages Concerned | |
| Development | 125 | 1998 | 3607-3614 | |
| Author | Title of Article | |||
| Yuasa, T., Ohno, S., Kehrl, J. H. and Kyriakis, J. M. | Tumor necrosis factor signaling to stress-activated protein kinase(SAPK)/Jun NH2-terminal kinase(JNK)and p38. Germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein associates with a mitogen-activated protein kinase kinase kinase upstream of MKK6 and p38. | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Biol. Chem. | 273 | 1998 | 22681-22692 | |
| Author | Title of Article | |||
| Nyui, N., Tamura, K., Mizuno, K., Ishigami, T., Kihara, M., Ochiai, H., Kimura, K., Umemura, S., Ohno, S., Taga, T. and Ishii, M. | gp130 is involved in stretch-induced MAP kinase activation in cardiac myocytes. | |||
| Journal | Volume | Year | Pages Concerned | |
| Biochem. Biophys. Res. Commun. | 245 | 1998 | 928-932 | |
| Author | Title of Article | |||
| Hirai, S-I., Noda, K., Moriguchi, T., Nishida, E., Yamashita, A., Deyama, T., Fukuyama, K. and Ohno, S. | Differential activation of two JNK activators, MKK7 and SEK1, by MKN28-derived nonreceptor serine/threonine kinase/mixed lineage kinase 2. | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Biol. Chem. | 273 | 1998 | 7406-7412 | |
| Author | Title of Article | |||
| Suzuki, A., Sugiyama, Y., Hayashi, Y., Nyu-i, N., Yoshida, M., Nonaka, I., Ishiura, S., Arahata, K. and Ohno, S. | MKBP, a novel member of the small heat shock protein family, binds and activates the myotonic dystrophy protein kinase(DMPK). | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Cell Biol. | 140 | 1998 | 1113-1124 | |
| Author | Title of Article | |||
| Zhuang, S., Hirai, S-I, Mizuno, K., Suzuki, A., Akimoto, K., Izumi, Y., Yamashita, A. and Ohno, S. | Involvement of protein kinase C in the activation of extracelluar signal-regulated kinase 1/2 by UVC irradiation. | |||
| Journal | Volume | Year | Pages Concerned | |
| Biochem. Biophys. Res. Commun. | 240 | 1997 | 273-278 | |
| Author | Title of Article | |||
| Ichimura, T., Ito, M., Itagaki, C., Takahashi, M., Horigome, T., Omata, S., Ohno, S. and Isobe, T. | The 14-3-3 protein binds its target proteins with a common site located towards the C-terminus. | |||
| Journal | Volume | Year | Pages Concerned | |
| FEBS Letter | 413 | 1997 | 273-276 | |
| Author | Title of Article | |||
| Mizuno, K., Noda, K., Araki, T., Imaoka, T., Kobayashi, Y., Akita, Y., Shimonaka, M., Kishi, S. and Ohno, S. | The proteolytic cleavage of protein kinase C isotypes, which generates kinase and regulatory fragments, correlates with Fas-mediated and 12-0-tetradecanoyl-phorbol-13-acetate-induced apotosis. | |||
| Journal | Volume | Year | Pages Concerned | |
| Eur. J., Biochem. | 250 | 1997 | 7-18 | |
| Author | Title of Article | |||
| Nyui, N, Tamura, K., Mizuno, K., Ishigami, T., Hibi, K., Yabana, M., Kihara, M., Fukamizu, A., Ochiai, H., Umemura, S., Murakami, K., Ohno, S. and Ishii, M. | Stretch-induced map kinase activation in cardiomyocytes of angiotensinogen-deficientmice. | |||
| Journal | Volume | Year | Pages Concerned | |
| Biochem. Biophys. Res. Commun. | 233 | 1997 | 36-41 | |
| Author | Title of Article | |||
| Osada, S., Izawa, M., Saito, R., Mizuno, K., Suzuki, A., Hirai, S. and Ohno. S. | YSK1, a novel mammalian protein kinase structurally related to Ste20 and SPS1, but not involved in the known MAPK pathways. | |||
| Journal | Volume | Year | Pages Concerned | |
| Oncogene | 14 | 1997 | 2047-2057 | |
| Author | Title of Article | |||
| Lu, Z., Hornia, A., Jiang, Y-W., Frankel, P., Zang Q., Ohno, S. and Foster, D. A. | Tumor-promotion by depleting cells of protein kinase Cd. | |||
| Journal | Volume | Year | Pages Concerned | |
| Molecular and Cellular Biol. | 17 | 1997 | 3418-3428 | |
| Author | Title of Article | |||
| Fukumoto, S., Nishizawa, Y., Hosoi, M., Koyama, H., Yamakawa, K., Ohno, S. and Morii, H. | Protein kinase C delta isoform inhibits the proliferation of vascular smooth muscle cells through suppressiong G1 cyclins expression. | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Biol. Chem. | 272 | 1997 | 13816-13822 | |
| Author | Title of Article | |||
| Hirai, S., Katoh, M., Terada, M., Kyriakis, J. M., Zon, L. I., Avruch, J. and Ohno, S. | MST/MLK2, a member of the mixed lineage kinase family, directly phosphorylates and activates SEK1, an activator of JNK/SAPK. | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Biol. Chem. | 272 | 1997 | 15167-15173 | |
| Author | Title of Article | |||
| Izumi, Y., Hirai, S., Tamai, Y., Fujise-Matsuoka, A., Nishimura, Y. and Ohno, S. | A protein kinase C delta-binding protein SRBC whose expression is induced by serum starvation. | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Biol. Chem. | 272 | 1997 | 7381-7389 | |
| Author | Title of Article | |||
| Osada, S., Izawa, M., Koyama, T., Hirai, S. and Ohno, S. | A domain containing the Cdc42/Rac interactive binding(CRIB)region of p65PAK inhibits transcriptional activation and cell transformation mediated by the Ras-Rac pathway. | |||
| Journal | Volume | Year | Pages Concerned | |
| FEBS Letter | 404 | 1997 | 227-233 | |
| Author | Title of Article | |||
| Ohno, S. | The distinct biological potential of PKC isotypes. | |||
| Journal | Volume | Year | Pages Concerned | |
| Protein Kinase C | 1997 | 75-93 | ||
| Author | Title of Article | |||
| Chalfant, C. E., Ohno, S., Konno, Y., Fisher, A. A., Watson, J. E. and Cooper, D. R. | A carboxy-terminal deletion mutant of PKCbeta II inhibits insulin-stimulated 2-deoxyglucose uptake in rat L6 skeletal muscle cells. | |||
| Journal | Volume | Year | Pages Concerned | |
| Molecular Endocrinology | 10 | 1996 | 1273-1281 | |
| Author | Title of Article | |||
| Ueda, Y., Hirai, S., Osada, S., Suzuki, A., Mizuno, K. and Ohno, S. | Protein kinase C d activates the MEK-ERK pathway in a manner independent of Ras and dependent on Raf. | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Biol. Chem. | 271 | 1996 | 23512-23519 | |
| Author | Title of Article | |||
| Rana, A., Gallo, K., Godowski, P., Hirai, S., Ohno, S., Zon, L., Kyriakis, J. M. and Auruch, J. | The mixed lineage kinase SPRK phosphorylates and activates the stress-activated protein kinase activator, SEK-1. | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Biol. Chem. | 271 | 1996 | 19025-19028 | |
| Author | Title of Article | |||
| Nakaigawa, N., Hirai, S.-I., Mizuno, K., Suzuki, A., Shuin, T., Hosaka, M. and Ohno, S. | Differential effects of overexpression of PKC α and PKC δ/ε on cellular E2F activity at late G1 phase. | |||
| Journal | Volume | Year | Pages Concerned | |
| Biochem. Biophys. Res. Commun. | 222 | 1996 | 93-100 | |
| Author | Title of Article | |||
| Hirano, M., Osada, S., Aoki, T., Hirai, S., Hosaka, M., Inoue, J., and Ohno, S. | MEK kinase is involved in TNFa-mediated activation of NFkB and degradation of IkBa. | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Biol. Chem. | 271 | 1996 | 13324-13238 | |
| Author | Title of Article | |||
| Ueda, E., Ohno, S., Kuroki, T., Livneh, E., Yamada, K., Yamanishi, K., Yasuno, H. | The h isoform of protein kinase C mediates transcriptional activation of the human transglutaminase 1 gene. | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Biol. Chem. | 271 | 1996 | 9790-9794 | |
| Author | Title of Article | |||
| Akimoto, K., Takahashi, R., Moriya, S., Nishioka, N., Takayanagi, J., Kimura, K., Fukui, Y., Osada, S., Mizuno, K., Hirai, S., Kazlauskas, A. and Ohno, S. | EGF and PDGF receptors activate atypical PKC1 through phosphatidylinositol 3-kinase. | |||
| Journal | Volume | Year | Pages Concerned | |
| EMBO J. | 15 | 1996 | 788-798 | |
| Author | Title of Article | |||
| Hirai, S., Izawa, N., Osada, S., Spyrou, G. and Ohno, S. | Activation of the JNK pathway by distantly related protein kinases, MEKK and MUK. | |||
| Journal | Volume | Year | Pages Concerned | |
| Oncogene. | 12 | 1996 | 641-630 | |
| Author | Title of Article | |||
| Moriya, S., Kazlauskas, A., Akimoto, K., Hirai, S., Mizuno, K., Takenawa, T., Fukui, Y., Watanabe, Y., Ozaki, S. and Ohno, S. | PDGF activates protein kinase Ce through redundant and independent signaling pathways involving phosphpholipase Cg or phosphatidylinositol 3-kinase. | |||
| Journal | Volume | Year | Pages Concerned | |
| Proc Natl. Acad. Sci. U. S. A. | 93 | 1996 | 151-155 | |