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1997 Fiscal Year Annual Research Report

プロテインキナーゼCとその基質タンパク質との特異的相互作用を操作する技術の開発

Research Project

Project/Area Number 09558088
Research InstitutionYokohama City University

Principal Investigator

大野 茂男  横浜市立大学, 医学部, 教授 (10142027)

Co-Investigator(Kenkyū-buntansha) 水野 恵子  横浜市立大学, 医学部, 助手 (90221803)
鈴木 厚  横浜市立大学, 医学部, 助手 (00264606)
KeywordsプロテインキナーゼC / 細胞極性 / 上皮細胞 / 増殖 / がん
Research Abstract

プロテインキナーゼC(PKC)の結合タンパク質として見いだしたASIP(aPKC speciffic interacting protein)は、PDZドメインを3個、aPKC結合部位などの特徴的な配列を有する。分子全体が線虫の細胞極性を支配する遺伝子と極めて相似の構造を示したことから、線虫におけるaPKCを検索しそれを見いだした。更に、線虫のaPKCが実際に細胞極性を支配し、線虫の初期発生の細胞分裂の不均等性を支配していることが明らかとなった。この結果を踏まえ、ほ乳類細胞におけるASIPとaPKCの機能を解析したところ、上皮細胞において、両者が細胞接着部位に極性を持って局在していることを見いだした。上皮細胞は極性を有することがその生理機能発揮に必須であり、その異常は増殖異常、つまりがんの一因と考えられている。つまり、aPKCの示す増殖制御機能の少なくとも一端は細胞の極性制御にあることがわかった事になる。興味深いことに、ASIPとaPKCの特異的な複合体は、線虫でも、ほ乳類の上皮細胞でも、細胞膜直下に存在する。更にこれら以外のタンパク質とも相互作用して巨大なシグナル複合体を構成していることが推測されるに至った。このシグナル複合体の構成分子を解析することが、細胞の極性制御の理解に極めて有効であろうと推測される。

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] 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." J.Biol.chem.(in press).

  • [Publications] Suzuki,A., Sugiyama,Y., Hayashi,Y., Nyui,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)." J.Cell.Biol.(in press).

  • [Publications] 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." Biochem.Biophys.Res.Commun.240. 273-278 (1997)

  • [Publications] 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." FEBS Letter. 413. 273-276 (1997)

  • [Publications] Oka,N., Yamamoto,M., Schwencke,C., Kawabe,J-I., Ebina,T., Ohno,S., Couet,J., Lisanti,M.P.and Ishiwaka,Y.: "Caveolin interaction with protein kinase C." J.Biol.Chem.272. 33416-33421 (1997)

  • [Publications] 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 apotpses." Eur.J.,Biochem.250. 7-18 (1997)

  • [Publications] 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 angiotensinogendeficient mice." Biochem.Biophys.Res.Commun.235. 36-41 (1997)

  • [Publications] 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." Oncogene. 14. 2047-2057 (1997)

  • [Publications] Kitamura,Y., Kitamura,T., Sakaue,H., Maeda,T., Ueno,H., Nishio,S., Ohno,S., Osada,S., Sakaue,M., Ogawa,W.and Kasuga,M.: "Interaction of Nck-associated protein 1 with activated GTP-binding protein Rac." Biochem.J.322. 873-878 (1997)

  • [Publications] Ebina,T., Kawabe,J., Katada,T., Ohno,S., Homcy,C,J.and Ishikawa,Y.: "Conformation-dependentactivation of type II adenylylcyclase by protein kinase C." J.Cell Biochem.64. 492-498 (1997)

  • [Publications] Lu,Z., Homia,A., Jiang,Y-W., Frankel,P., Zang Q., Ohno,S.and Foster,D.A.: "Trmor-promotion by depleting cells of protein kinase Cδ." Molecular and Cellular Biol.17. 3418-3428 (1997)

  • [Publications] 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." J.Biol.Chem.272. 13816-13822 (1997)

  • [Publications] Hirai,S., Katoh,M., Terada,M., Kyriakis,J.M., Zon,L.L., 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." J.Biol.Chem.272. 15167-15173 (1997)

  • [Publications] 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." J.Biol.Chem.272. 7381-7389 (1997)

  • [Publications] 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 Ras-Rac pathway." FEBS Letter. 404. 227-233 (1997)

  • [Publications] Ohno,S.: "The distinct biological potential of PKC isotypes." in Protein Kinase C. 75-93 (1997)

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Published: 1999-03-15   Modified: 2016-04-21  

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