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Studies on signal transduction in generation and development of cancers.

Research Project

Project/Area Number 10460037
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用微生物学・応用生物化学
Research InstitutionThe University of Tokyo

Principal Investigator

FUKUI Yasuhisa  Grad. Sch. Agriculture and Life Science, Univ. of Tokyo, Prof., 大学院・農学生命科学研究科, 教授 (00181248)

Co-Investigator(Kenkyū-buntansha) NAGATA Satoshi  Grad. Sch. Agriculture and Life Science, Univ. of Tokyo, Lecturer, 大学院・農学生命科学研究科, 講師 (40246682)
IHARA Sayoko  Grad. Sch. Agriculture and Life Science, Univ. of Tokyo, Pfor., 大学院・農学生命科学研究科, 助手 (80292788)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥12,600,000 (Direct Cost: ¥12,600,000)
Fiscal Year 1999: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 1998: ¥8,500,000 (Direct Cost: ¥8,500,000)
Keywordsphospholipids / phosphatidylinositol kinase / cell response / differentiation / adapter / polyphosphoinositides / MAP kinase / phospholipase / イノシトールリン脂質 / ホスファチジルイノシトール / ホスファチジルイノシトール3キナーゼ / 細胞応答 / 細胞増殖 / 細胞分化 / 増殖因子 / 分化因子
Research Abstract

Phosphatodylinosito1 3-kinase is the enzyme that produces PIPィイD23ィエD2 in vivo. PIP3ィイD2aィエD2 acts as an important second messenger to activate various downstream factors. However, despite the efforts of a number of laboratories, there are not enough downstream factors identified to explain variety of cell responses dependent of PI 3-kinase pathway. We have produced PIPィイD23ィエD2 analogue beads and used them for identification of PIPィイD23ィエD2 binding proteins, which are the candidates for the downstream factors of PIPィイD23ィエD2 PIP3BP is one of such PIPィイD23ィエD2 binding proteins which localizes in the nucleus. Since it is homologous to Arf-GAP, it is likely that this protein is involved in vesicle transport. This year, we established hybridoma lines which produce BP-kinesin, a binding protein for PIP3B. We also identified SWAP70 as a PIPィイD23ィエD2 binding protein which is suggested to be a subunit of a B-cell specific recombinase complex. SWAP70 localized in the cytoplasm but moved into nucleus when co-expressed with a constitutively active PI 3-kinase. This translocation was sensitive to wortmannin, PI 3-kinase inhibitor. SWAP70 was overexpressed in Sf9 cells and purified. In vitro analysis for nuclear translocation revealed that SWAP70 is impo1-ted to the nucleus in an ATP dependent manner. It is of interest to test the role of in this PIPィイD23ィエD2 System.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (48 results)

All Other

All Publications (48 results)

  • [Publications] Fukui, Y., et al.: "Downstream of phosphatidylinositol-3 kinase, a multifunctional signaling molecule, and its regulation in cell responses"J. Biochem. 124. 1-7 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fukui, Y., et al.: "Specific detection of phosphatidylinositol 3,4,5-trisphosphate binding proteins by the PIP3 analogue beads: an application for rapid purification of the PIP3 binding proteins"Biochim Biophys Acta. 24. 292-302 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fukui, Y., et al.: "Microinjection of activated phosphatidylinositol-3 kinase induces process outgrowth in rat PC12 cells through the Rac-JNK signal transduction pathway"J Cell Sci.. 111. 907-915 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fukui, Y., et al.: "Density dependent elevation of phosphatidylinositol-3 kinase level in rat 3Y1 cells"Biochim Biophys Acta. 1401. 113-120 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fukui, Y., et al.: "Synthesis of diacylglycerol analogs of phosphatidylinositol 3,4,5-trisphosphate"Tetrahed. Let.. 39. 9485-9488 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fukui, Y., et al.: "Dedifferentiation of Adenocarcinomas by Activation of Phosphatidylinositol 3-kinase"Proc Natl Acad Sci USA. 96. 4874-4879 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fukui, Y., et al.: "The structural requirement of phosphatidylinositols as substrate of phosphatidylinositol 3-kinase"Tetrahed. Let.. 40. 1693-1696 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fukui, Y., et al.: "Cyclin DI expression mediated by phosphatidylinositol 3-kinase through mTOR-p70S6K-independent signaling in growth factor-stimulated NIH3T3 fibroblasts"Mol. Cell. Biol.. 19. 1346-1358 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fukui, Y., et al.: "Increased insulin sensitivity and hypoglycemia in mice lacking p85a regulatory subunit of phosphoinositide 3-kinase"Nat. Genet.. 21. 230-235 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fukui, Y., et al.: "An evidence that a phosphatidylinositol 3,4,5-trisphosphate binding protein can function in nucleus"J. Biol Chem. 274. 3919-3922 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fukui, Y., et al.: "Identification of protein kinase B (PKB) as a phosphatidylinositol 3,4,5-trisphosphate binding protein in Dictyostelium discoideum"Biosci. Biotech. Biochem.. 63. 368-372 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fukui, Y., et al.: "Adenoviral gene transfer of activated phosphatidylinositol 3'-kinase and Akt inhibits apoptosis of hypoxic cardiomyocytes in vitro"Circulation. 100. 2373-9 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fukui, Y., et al.: "Dedifferentiation of adenocarcinomas by activation of phosphatidylinositol 3-kinase"Proc. Natl Acad Sci USA. 96. 4874-9 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fukui, Y., et al.: "In vitro and in vivo suppression of osteoclast function by adenovirus vector-induced csk gene"J Bone Miner Res.. 15. 41-51 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fukui Y, Ihara S, Nagata S: "Downstream of phosphatidylinositol-3 kinase, a multifunctional signaling molecule, and its regulation in cell responses."J Biochem.. 124. 1-7 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shirai T, Tanaka K, Terada Y, Sawada T, Shirai R, Hashimoto Y, Nagata S, Iwamatsu A, Okawa K, Li S, Hattori S, Mano H, Fukui Y.: "Specific detection of phosphatidylinositol 3, 4, 5-trisphosphate binding proteins by the PIP3 analogue beads : an application for rapid purification of the PIP3 binding proteins."Biochim Biophys Acta.. 1402. 292-302 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kita Y, Kimura KD, Kobayashi M, Ihara S, Kaibuchi K, Kuroda S, Ui M, Iba H, Konishi H, Kikkawa U, Nagata S, Fukui Y.: "Microinjection of activated phosphatidylinositol-3 kinase induces process outgrowth in rat PC12 cells through the Rae-JNK signal transduction pathway."J Cell Sci.. 111. 907-915 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Daduang S, Kimura K, Nagata S, Fukui Y.: "Density dependent elevation of phosphatidylinositol-3 kinase level in rat 3Y1 cells."Biochim Biophys Acta.. 1401. 113-120 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kobayashi W, Nagata S, Iwasaki T, Yanagihara K, Saitoh I, Karouji Y, Ihara S, Fukui Y.: "Differentiation of adenocarcinomas by activation of phosphatidylinosito1 3-kinase."Proc Natl Acad Sci U S A.. 96. 4874-4879 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tanaka A, Adachi H, Konishi H, Iwamatsu A, Ohkawa K, Shirai T, Nagata S, Kikkawa U, Fukui Y.: "Identification of protein kinase B (PKB) as a phosphatidylinositol 3, 4, 5-trisphosphate binding protein in Dictyostelium discoideum."Biosci Biotechnol Biochem. 63. 368-372 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tanaka A, Horiguchi K, Yoshida T, Takeda W, Fujisawa H, Takeuchi K, Umeda M, Kato S, Ihara S, Nagata S, Fukui Y.: "Evidence that a phosphatidylinositol 3, 4, 5-trisphosphate-binding protein can function in nucleus."J Biol Chem.. 274. 3919-3922 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shirai, R., Morita, K., Nishikawa, A., Nakatsu, N., Fukui, Y., Morisaki, N., Hishimoto, Y.: "Synthesis of diacylglycerol analogs of phosphatidylinosito1 3, 4, 5-trisphosphate."Tetrahed. Let.. 39. 9485-9488 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takuwa, N., Fukui, Y., Takuwa, Y.: "Cyclin D1 expression mediated by phosphatidyl-inositol 3-kinase through mTOR-p70S6K-independent signaling in growth factor-stimulated NIH3T3 fibroblasts."Mol. Cell. Biol.. 19. 1346-1358 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Terauchi, Y., Tsuji, Y., Satoh, S., Minoura, H., Murakami, K., Okuno, A., Inukai, K., Asano, T., Kaburagi, K., Ueki, H., Y., Nakajima, T., Hanafusa, Y., Matsuzawa, H., Sekihara, Y., YinJ., C., Barrett, J., Backer, H., Ishikawa, Y., Akanuma, I., Komuro, M., Suzuki, K., Yamamura, T., Kodama, H., Suzuki, S., Koyasu, S., Aizawa, K., Tobe, Y., Fukui, Y., Yazaki, Y., Kadowaki T.: "Increased insulin sensitivity and hypoglycemia in mice lacking p85a regulatory subunit of phosphoinositide 3-kinase."Nat. Genet.. 21. 230-235 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shirai, R., Morita, K., Nishikawa, A., Nakatsu, N., Fukui, Y., Morisaki, N., Hashimoto, Y.: "The structural requirement of phosphatidylinositols as substrate of phosphatidylinositol 3-kinase."Tetrahed. Let.. 40. 1693-1696 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsui, T, LiL, del Monte F, Fukui, Y, Franke, TF, Hajjar, RJ, Rosenzweig, A.: "Adenoviral gene transfer of activated phosphatidylinositol 3'-kinase and Akt inhibits apoptosis of hypoxic cardiomyocytes in vitro."Circulation. 100. 2373-2379 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Konishi, H, Fujiyoshi, T, Fukui, Y, Matsuzaki, H, Yamamoto, T, Ono, Andjelkovic, M, Hemmings, BA, Kikkawa, U: "Activation of protein kinase B induced by H (2)O(2) and heat shock through distinct mechanisms dependent and independent of phosphatidylinositol 3-kinase."J Biochem.. 126. 1136-1143 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Miyazaki, T, Takayanagi, H, Isshiki, M, Takahashi, T, Okada, M, Fukui, Y., Oda, H, Nakamura, K, Hirai, H, Kurokawa, T, Tanaka, S.: "In vitro and in vivo suppression of osteoclast function by adenovirus vector-induced csk gene."J Bone Miner Res.. 15. 41-51 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fukui,Y.,et al.: "Downstream of phosphatidylinositol-3 kinase,a multifunctional signaling molecule,and its regulation in cell responses"J.Biochem. 124. 1-7 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fukui,Y.,et al.: "Specific detection of phosphatidylinositol 3,4,5-trisphosphate binding proteins by the PIP3 analogue beads : an application for rapid purification of the PIP3 binding proteins"Biochim Biophys Acta.. 24. 292-302 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fukui,Y.,et al.: "Microinjection of activated phosphatidylinositol-3 kinase induces process outgrowth in rat PC12 cells through the Rac-JNK signal transduction pathway"J Cell Sci.. 111. 907-915 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fukui,Y.,et al.: "Density dependent elevation of phosphatidylinositol-3 kinase level in rat 3Yl cells"Biochim Biophys Acta.. 1401. 113-120 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fukui,Y.,et al.: "Synthesis of diacylglycerol analogs of phosphatidylinositol 3,4,5-trisphosphate"Tetrahed.Let.. 39. 9485-9488 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fukui,Y.,et al.: "Dedifferentiation of Adenocarcinomas by Activation of Phosphatidylinositol 3-kinase"Proc Natl Acad Sci USA. 96. 4874-4879 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fukui,Y.,et al.: "The structural requirement of phosphatidylinositols as substrate of phosphatidylinositol 3-kinase"Tetrahed.Let.. 40. 1693-1696 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fukui,Y.,et al.: "Cyclin D1 expression mediated by phosphatidylinositol 3-kinase through mTOR-70S6K-independent signaling in growth factor-stimulated NIH3T3 fibroblasts"Mol.Cell.Biol.. 19. 1346-1358 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fukui,Y.,et al.: "Increased insulin sensitivity and hipoglycemia in mice lacking p85a regulatory subunit of phosphoinositide 3-kinase"Nat.Genet.. 21. 230-235 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fukui,Y.,et al.: "An evidence that a phosphatidylinositol 3,4,5-trisphosphate binding protein can function in nucleus"J.Biol Chem.. 274. 3919-3922 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fukui,Y.,et al.: "Identification of protein kinasa B (PKB) as a phosphatidylinostitol 3,4,5-trisphosphate binding protein in Dictyostelium discoideum"Biosci.Biotech.Biochem.. 63. 368-372 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fukui,Y.,et al.: "Adenoviral gene transfer of activated phosphatidylinositol 3'-kinase and Akt inhibits apoptosis of hypoxic cardiomyocytes in vitro"Circulation. 100. 2373-2379 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fukui,Y.,et al.: "Dedifferentiation of adenocarcinomas by activation of phosphatidylinositol 3-kinasa"Proc Natl Acad Sci USA. 96. 4874-4879 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fukui,Y.,et al.: "In vitro and in vivo suppression of osteoclast function by adenovirus vector-induced csk gene"J.Bone Miner Res.. 15. 41-51 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kita, Y.et al.: "Microinjection of activated phosphatidylinositol-3 kinase induces precess outgrowth in rat PC12 cells through the Tac-JNK signal transduction pathway." J.Cell.Sci.111. 907-915 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shirai,T.et al.: "Specific detection of phosphatidylinositol 3,4,5-trisphosphate binding proteins by the PIP3 analogue beads:An application for rapid purification of the PIP3 binding proteins" Biochem.Biophys.Acta. 1402. 292-302 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fukui, Y.et al.: "Downstream of phosphatidylinositol-3 kinase, a multifunctional signaling molecule, and its regulation in cell responses." J.Biochem.124. 1-7 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takawa, N.et al.: "Cyclin D1 expression mediated by phosphatidylinositol 3-kinase through mTOR-p70^<S6K>-independent signaling in growth factor-stimulated NIH3T3 fibroblasts." Moll.Cell.Biol.(in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tanaka, K.et al.: "Identification of protein kinase B(PKB)as a phosphatidylinositol 3,4,5-trisphosphate binding protein in Dictyostelium discoideum." Biosci.Biotech.Biochem.(in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tanaka, K.et al.: "An evidence that a phosphatidylinositol 3,4,5-trisphosphate binding protein can function in nucleus." J.Biol.Chem.(in press). (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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