細胞膜裏打ち蛋白質による足場依存的細胞増殖と浸潤の制御

• Project/Area Number: 13216050
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyoto University
• Principal Investigator: 木岡 紀幸 京都大学, 農学研究科, 助教授 (90234179)
• Co-Investigator(Kenkyū-buntansha): 松尾 道憲 京都大学, 農学研究科, 助手 (00335308) ; 中西 宏之 熊本大学, 医学部, 教授 (80314318)
• Project Period (FY): 2002 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥53,000,000 (Direct Cost: ¥53,000,000); Fiscal Year 2004: ¥17,000,000 (Direct Cost: ¥17,000,000); Fiscal Year 2003: ¥17,000,000 (Direct Cost: ¥17,000,000); Fiscal Year 2002: ¥9,000,000 (Direct Cost: ¥9,000,000); Fiscal Year 2001: ¥10,000,000 (Direct Cost: ¥10,000,000)
• Keywords: 細胞密着 / 細胞骨格 / アクチン / ビネキシン / ビンキュリン / 足場依存性 / 細胞接着 / 裏打ち蛋白質 / 増殖シグナル / MARK

Research Abstract

細胞接着による細胞増殖や細胞運動の制御機構を明らかにするために、細胞接着領域に集積する裏打ち蛋白質に着目し、解析を行ってきた。今年度はこれまでに報告してきたビネキシンによるERK活性化の足場非依存性誘導について、そのメカニズムの解析を行った。その結果ビネキシンはNIH3T3細胞内で、ERKの活性化因子を調節するのではなく、不活性化因子、つまりフスファターゼによるERKの不活性化を抑制していることを明らかにした。しかもこの不活性化の抑制にはビネキシンとERKとの直接結合が重要であること、ERK特異的フォスファターゼであるMKP3の強制発現によって解除されることが明らかとなった。また、ビネキシンによって、EGFR活性化が維持増幅されること、および、v-srcがん細胞におけるビネキシンの発現調節機構についても明らかにした。(木岡)
また、Tubulin blot overlay法と微小管共沈法によって、新しい微小管結合蛋白質p90とp100(仮命名)を同定した。p90は微小管のbundling活性を示し、p100はRac低分子量G蛋白質の下流で機能し、チュブリンの重合を促進することを見出した。(中西)

Research Products

• [Journal Article] Extracellular Signal-regulated Kinase Activated by Epidermal Growth Factor and Cell Adhesion Interacts with and Phosphorylates Vinexin. (2004)
  • Author(s): Mitsushima, M., Suwa, A., Amachi, T., Ueda K., Kioka N.
  • Journal Title: J Biol Chem 279 Pages: 34570-34577
• [Journal Article] Alpha1-syntrophin modulates turnover of ABCA1 (2004)
  • Author(s): Munehira, Y., Ohnishi, T., Kawamoto, S., Furuya, A, Shitara, K, Imamura M., Yokota, T., Takeda S., Amachi, T., Matsuo, M., Kioka, N., Ueda, K.
  • Journal Title: J Biol Chem 279 Pages: 15091-15095
• [Journal Article] ATP hydrolysis-dependent multidrug efflux transporter : MDR1/P-glycoprotein. (2004)
  • Author(s): Kimura, Y., Matsuo, M., Takahashi, K., Saeki, T., Kioka, N., Amachi, T., Ueda, K
  • Journal Title: Drug Metab 5 Pages: 1-10
• [Journal Article] Human ABCA3, a product of a responsible gene for abca3 for fatal surfactant deficiency in newborns, exhibits unique ATP hydrolysis activity and generates intrarcellular multilamellar vesicles (2004)
  • Author(s): Nagata, K., Yamamoto, A., Ban, N., Tanaka, A.R., Matsuo, M., Kioka, N., Inagaki, N., Ueda, K.
  • Journal Title: Biochem Biophys Res Commun 324 Pages: 262-268
• [Publications] Wakabayashi, M., Ito, T., Mitsushima, M., Aizawa, S., Ueda, K., Amachi, T., Kioka, N: "Interaction of 1p-dlg/KIAA0583, a membrane-associated guanylate kinase family protein, with vinexin and beta-catenin at sites of cell-cell contact"J Biol Chem. 278. 21709-21714 (2003)
• [Publications] Townson, S., Dobrzycka, K.M., Lee, A.V., Air, M., Deng, W., Kang, K., Jiang, S., Kioka, N., Michaelis, K., Oesterreich, S.: "SAFB2 - A new SAFB homolog and estrogen receptor corepressor."J Biol Chem. 278. 20059-20068 (2003)
• [Publications] Umehara, H., Nishii, Y., Morishima, M., Kakehi, Y., Kioka, N., Amachi, T., Koizumi, J., Hagiwara, M., Ueda, K: "Effect of cisplatin treatment on speckled distribution of a serine/arginine-rich nuclear protein CROP/Luc7A"Biochem Biophys.Res Commun. 301. 324-329 (2003)
• [Publications] Tanaka A.R., Abe-Dohmae, S., Ohnishi, T., Aoki, R., Morinaga, G., Okuhira, K., Ikeda, Y., Kano, F., Matsuo M., Kioka, N., Amachi T., Murata, M., Yokoyama, S., Ueda, K: "Effects of mutations of ABCA1 in the first extracellular domain on subcellular trafficking and ATP binding/hydrolysis"J Biol Chem. 278. 8815-8819 (2003)
• [Publications] Ikeda, Y., Aba-Dohmae.S., Munehira, Y., Aoki, R., Kawamoto, S., Furuya.A., Shitara, K., Amachi, T., Kioka, N., Matsuo, M., Yokoyama, S., Ueda, K.: "Post-transcriptional regulation of human ABCA7 and its function for the apoA-I-dependent lipid release"Biochem Biophys Res Commun. 311. 313-318 (2003)
• [Publications] Fukada, T., Ono, M., Sakata, S., Kioka, N., Sakai, H., Komano, T.: "Genomic structure and 5'-flanking sequences of rat N-acetylglucosaminyltransferase I gene and regulatory role of its transcriptional diversity."Biosci Biotechnol Biochem. 67. 1515-1521 (2003)
• [Publications] Suwa, A., Mitsushima, M., Ito, T., Akamatsu, M., Ueda, K., Amachi, T., Kioka, N.: "Vinexin beta Regulates the Anchorage Dependence of ERK2 Activation Stimulated by Epidermal Growth Factor"J Biol Chem. 277. 13053-13058 (2002)
• [Publications] Kioka, N., Ueda, K., Amachi, T: "Vinexin, CAP/ponsin, ArgBP2 : a Novel Adaptor Protein Family Regulating Cytoskeletal Organization and Signal Transduction"Cell Struct Funct. 27. 1-7 (2002)
• [Publications] Tanaka, A.R., Abe-Dohmae, S., Ohnishi, t., Aoki, R., Morinaga, G., Okuhira, K.I., Ikeda, Y., Kano, F., Matsuo, M., Kioka, N., Amachi, T., Murata, M., Yokoyama, S., Ueda, K.: "Effects of mutations of ABCA1 in the first extracellular domain on subcellular trafficking and ATP binding/hydrolysis"J Biol Chem. 278. 8815-8819 (2003)
• [Publications] Umehara, H., Nishii, Y., Morishima, M., Kakehi, Y., Kioka, N., Amachi, T., Koizumi, J., Hagiwara, M., Ueda, K.: "Effect of cisplatin treatment on speckled distribution of a serine/arginine-rich nuclear protein CROP/Luc7A"Biochem Biophys Res Commun. 301. 324-329 (2003)
• [Publications] Tanaka, A.R., Tanabe, K., Morita, M., Kurisu, M., Kasiwayama, Y., Matsuo, M., Kioka, N., Amachi, T., Imanaka, T., Ueda, K.: "ATP binding/hydrolysis by and phosphorylation of peroxisomal ATP-binding cassette proteins PMP7O (ABCD3) and adrenoleukodystrophy protein (ABCD1)"J Biol Chem. 277. 40142-40147 (2002)
• [Publications] Suwa, A., M.Mitsushima, T.Ito, M.Akamatsu, K.Ueda, T.Amachi, N.Kioka: "Vinexin beta regulates anchorage dependence of ERK2 activation stimulated by epidermal growth factor"J Biol Chem. (印刷中). (2002)
• [Publications] Kawauchi, T., M.Ikeya, S.Takada, K.Ueda, M.Shirai, Y.Takihara, N.Kioka, T.Amachi: "Expression of vinexin alpha in the dorsal half of the eye and in the cardiac outflow tract and atrioventricular canal"Mech Dev. 106. 147-150 (2001)
• [Publications] Tanaka, A.R, Y.Ikeda, S.Abe-Dohmae, R.Arakawa, K.Sadanami, A.Kidera, S.Nakagawa, T.Nagase, R.Aoki, N.Kioka, T.Amachi, S.Yokoyama, K.Ueda: "Human ABCA1 contains a large amino-terminal extracellular domain homologous to an epitope of Sjogren's Syndrome"Biochem Biophys Res Commun. 283. 1019-1025 (2001)