哺乳類細胞の極性決定時におけるG蛋白質の役割とその制御機構

2006 Fiscal Year Annual Research Report

• Project/Area Number: 18057016
• Research Institution: Kyushu University
• Principal Investigator: 住本 英樹 九州大学, 生体防御医学研究所, 教授 (30179303)
• Co-Investigator(Kenkyū-buntansha): 鎌倉 幸子 九州大学, 生体防御医学研究所, 助手 (80398081) ; 武谷 立 九州大学, 生体防御医学研究所, 助手 (50335981)
• Keywords: 蛋白質 / シグナル伝達 / 発生・分化 / 細胞極性

Research Abstract

極性形成に関わる2つの蛋白質複合体「Pins-Gαi複合体」と「Par-aPKC複合体」はindependentに働くわけではなく、ショウジョウバエではInscuteableというアダプター分子により結ばれ(クロストークし)協調して機能することが知られている。本研究の目的は、哺乳類細胞の極性形成にいて「Pins-Gαi複合体」や「Par-aPKC複合体」が果たす役割を明らかにし、その作用機構を解明することであるが、平成18年度は以下のような成果を得た。
(1)ショウジョウバエのInscuteableの1次配列情報をもとに、ヒトInscuteableのcDNAを単離した。ヒトInscuteableは、ショウジョウバエのホモログとアミノ酸相同性が25%と低いにもかかわらず、ヒトPins-Gαi複合体ともヒトPar-aPKC複合体とも結合でき、またPar3とPinsに同時に結合することから、ヒト「Pins-Gαi複合体」と「Par-aPKC複合体」を繋ぐ分子であることを明らかにした。
(2)酵母two-hybridスクリーニングにより、新規Par3結合蛋白質としてPar3BMP1(Par3-binding membrane protein1)を単離した。Par3BMP1は1回膜貫通型蛋白質であり、PDZ結合モチーフを介しPar3と結合した。Par3BMP1の過剰発現は上皮細胞のPar3のTJへの局在及びTJ形成(細胞極性形成)を阻害することから、膜蛋白質Par3BMP1が細胞内のC末端領域でPar3と結合し、TJへとリクルートすることが、細胞極性形成に重要であることを示した。

Research Products

• [Journal Article] Transient receptor potential (TRP) protein 7 acts as a G protein- activated Ca^<2+> channel mediating angiotensin II-induced myocardial apoptosis. (2007)
  • Author(s): Satoh, S, Tanaka, H., Ueda, Y., Oyama, J.I., Sugano, M., Sumimoto, H, Mori, Y., Makino, N.
  • Journal Title: Mol. Cell. Biochem. 294 Pages: 205-215
• [Journal Article] Interaction between the SH3 domains and C-terminal proline-rich region in NADPH oxidase organizer 1 (Noxo1). (2007)
  • Author(s): Yamamoto, A., Kami, K., Takeya, R., Sumimoto, H.
  • Journal Title: Biochem. Biophys. Res Commun. 352 Pages: 560-565
• [Journal Article] A regulated adaptor function of p40^<phox> : distinct p67phox membrane targeting by p40^<phox> and by p47^<phox>. (2007)
  • Author(s): Ueyama, T., Tatsuno, T., Kawasaki, T., Tsujibe, S., Shirai, Y., Sumimoto, H., Leto, T.L., Saito.N.
  • Journal Title: Mol. Biol. Cell 18 Pages: 441-454
• [Journal Article] Full-length p40^<phox> structure suggests a basis for regulation mechanism of its membrane binding. (2007)
  • Author(s): Honbou, K, Minakami, R., Yuzawa, S., Takeya, R., Suzuki, N.N., Kamakura, S., Sumimoto, H., Inagaki, F.
  • Journal Title: EMBO J. 26 Pages: 1176-1186
• [Journal Article] Nox1 redox-signaling mediates oncogenic Ras-induced disruption of stress fibers and focal adhesions by down-regulating Rho. (2007)
  • Author(s): Shinohara, M., Shang, W.H., Kubodera, M, Harada, S., Mitsushita, J., Kato, M., Miyazaki, H., Sumimoto, H., Kamata, T
  • Journal Title: J. Biol. Chem. 282(in press)
• [Journal Article] Direct involvement of the small GTPase Rac in activation of the superoxide-producing NADPH oxidase Nox1. (2006)
  • Author(s): Miyano, K., Ueno, N., Takeya, R., Sumimoto, H.
  • Journal Title: J. Biol. Chem. 281 Pages: 21857-21868
• [Journal Article] Activation of the superoxide-producing phagocyte NADPH oxidase requires co-operation between the tandem SH3 domains of p47^<phox> in recognition of a polyproline type II helix and an adjacent α-helix of p22^<phox>. (2006)
  • Author(s): Nobuhisa, I., Takeya, R., Ogura, K., Ueno, N., Kohda, D., Inagaki, F., Sumimoto, H.
  • Journal Title: Biochem. J. 396 Pages: 183-192
• [Journal Article] Regulation of superoxide-producing NADPH oxidases in nonphagocytic cells. (2006)
  • Author(s): Takeya, R., Ueno, N., Sumimoto, H.
  • Journal Title: Methods Enzymol. 406 Pages: 456-468
• [Journal Article] NMR solution structure of the tandem SH3 domains of p47^<phox> complexed with a p22^<phox>-derived proline-rich peptide. (2006)
  • Author(s): Ogura, K., Nobuhisa, I., Yuzawa, S., Takeya, R., Torikai, S., Saikawa, K., Sumimoto, H., Inagaki, F.
  • Journal Title: J. Biol. Chem. 281 Pages: 3660-3668
• [Journal Article] Two forms of human Inscuteable-related protein that links Par3 to the Pins homologues LGN and AGS3. (2006)
  • Author(s): Izaki, T., Kamakura, S., Kohjima, M., Sumimoto, H.
  • Journal Title: Biochem. Biophys. Res. Commun. 341 Pages: 1001-1006
• [Journal Article] Regulation of novel superoxide-producing NAD(P)H oxidases. (2006)
  • Author(s): Takeya, R., Sumimoto, H.
  • Journal Title: Antioxid. Redox Signal. 8 Pages: 1523-1532
• [Journal Article] Expression and function of Noxo1, an alternative splicing form of the NADPH oxidase organizer 1. (2006)
  • Author(s): Takeya, R., Taura M., Yamasaki, T., Naito, S., Sumimoto, H.
  • Journal Title: FEBS J. 273 Pages: 3663-3677
• [Journal Article] Phagocytosis-coupled activation of the superoxide-producing phagocyte oxidase, a member of the NADPH oxidase (Nox) family. (2006)
  • Author(s): Minakami, R., Sumimoto, H.
  • Journal Title: Int. J. Hematol. 84 Pages: 193-198
• [Journal Article] Expression of isoforms of NADPH oxidase components in rat pancreatic islets. (2006)
  • Author(s): Uchizono, U., Takeya, R., Iwase, M., Sasaki, N., Oku, M., Imoto, H., Iida, M., Sumimoto, H.
  • Journal Title: Life Sci. 80 Pages: 133-139
• [Journal Article] Crystallization and preliminary crystallographic analysis of p4O^<phox>, a regulatory subunit of NADPH oxidase. (2006)
  • Author(s): Honbou K, Yuzawa S, Suzuki NN, Fujioka Y, Sumimoto H, Inagaki F
  • Journal Title: Acta Crystallograph Sect F Struct Biol Cryst Commun. 62 Pages: 1018-1020
• [Journal Article] TRPC3 and TRPC6 are essential for angiotensin II-induced cardiac hypertrophy. (2006)
  • Author(s): Onohara, N., Nishida, M., Inoue, R., Kobayashi, H., Sumimoto, H., Sato, Y., Mori, Y., Nagao, T., Kurose, H.
  • Journal Title: EMBO J. 25 Pages: 5305-5316
• [Journal Article] Increased expression of gp91^<phox> homologues of NAD(P)H oxidase in the aortic media during chronic hypertension; involvement of the rennin-angiotensin system. (2006)
  • Author(s): Akasaki, T., Ohya Y., Kuroda, J., Eto K., Abe, I, Sumimoto, H., Iida, M.
  • Journal Title: Hypertens. Res. 29 Pages: 813-820
• [Book] 生体防御医学事典 (2007)
  • Author(s): 住本 英樹(共編者・共著者)
  • Publisher: 朝倉書店(印刷中)