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Attempt for regulating biologial activities by use of molecular recognition of SH2 and SH3 domains.

Research Project

Project/Area Number 07558091
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Structural biochemistry
Research InstitutionThe University of Tokyo

Principal Investigator

TAKENAWA Tadaomi  The University of Tokyo The Institute of Medical Science, Professor, 医科学研究所, 教授 (40101315)

Co-Investigator(Kenkyū-buntansha) FUKAMI Kiyoko  The University of Tokyo The Institute of Medical Science, Research Associate, 医科学研究所, 助手 (40181242)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 1997: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1996: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1995: ¥7,600,000 (Direct Cost: ¥7,600,000)
KeywordsN-WASP / Ash / Grb2 / filopodia / actin / tyrosine kinase / Grb2 / SH2ドメイン / SH3ドメイン / ホスホリパーゼCγ1 / SH_2ドメイン / SH_3ドメイン / ホスホリパーゼC_γ1
Research Abstract

We found an adaptor protein, Ash/Grb2 which transmits tyrosine kinase signals to downstream, resulting in activation of Ras. This protein has one SH2 and two SH3 domains. In this project, we attempted to clarify binding proteins to Ash/Grb2 SH3 domain, and then purified SH3-binding proteins from bovine brain. Among them, two proteins (150 kDa and 65 kDa proteins) were new. After cDNA clonings of these proteins, 150 kDa protein was found to be one of synaptojamin isozymes. On the other hand, 65 kDa protein was found to be homologous to Wiskott-Aldrich syndrome protein (WASP). We therefore named it N-WASP.N-WASP has a PH domain, GBD/CRIB motif, IQ motif, verprolin-like motif, cofilin-like motif and proline-rich sequences. It binds to Ash/Grb2 SH3 domain and is activated downstream of tyrosine kinases. Activated N-WASP polymerizes actin filament in Cdc42 dependent manner, resulting in filopodia formation.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] H.Yu, et al.: "Phosphatidylinosito 4,5-bisphosphate reverses the inhibition of RNA transcription caused by histon Hl" Eur.J.Biochem.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Miki, et al.: "Induction of filopodium formation by a WASP related actin depolymeriziing protein N-WASP" Nature. 391. 93-97 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Fukuoka, et al.: "Identification of N-WASP homologs in human and rat brain" Gene. 196. 43-48 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Takenawa, et al.: "Grb2/Ash-control of the Ras pathway and the cytoskeleton" Current Topic in Microbiol.Immunol.228. 325-342 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Itoh, et al.: "β-Tubulin binds Src homology 2 domains through a region different from the tyrosine-phosphorylated protein-recognizing site" J.Biol.Chem.271. 27931-27935 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Fukami, et al.: "Identification of a PIP2-bindingsite in chicken skeletal muscle α-actinin" J.Biol.Chem.271. 2646-2650 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Fukami, N.Sawada, T.Endo and T.Takenawa: "Identification of a PIP2-binding site in chicken skeletal muscle alpha-actinin" J.Biol.Chem.271. 2646-2650 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Itoh, K.Miura, H.Miki, and T.Takenawa: "beta-Tubulin binds Src homology 2 domains through a region different from the tyrosine-phosphorylated protein-recognizing site" J.Biol.Chem.271. 27931-27935 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Takenawa, H.Miki, and K.Matuoka: "Signaling through Grb2/Ash-control of the Ras pathway and the cytoskeleton" Current Topic in Microbiol. Immunol.228. 325-342 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Fukuoka, H.Miki, and T.Takenawa: "Identification of N-WASP homologs in human and rat brain" Gene. 196. 43-48 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Miki, T.Sasaki, Y.Takai and T.Takenawa: "Induction-of filopodium formation by a WASP related actin depolymeriziing protein N-WASP" Nature. 391. 93-97 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Yu, K.Fukami, Y.Watanabe, S.Ozaki and T.Takenawa: "Phosphatidylinositol 4,5-bisphosphate reverses the inhibition of RNA transcription caused by histon H1" Eur.J.Biochem.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Miki,H., et al.: "A tyrosine kinase signalling regulates WASP function,which is essential for megakaryocyte differentiation." Cell Grwoth & Differ.8. 195-202 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Houssa.B., et al.: "Cloniong of a novel human diacylglycerol kinase containing three cystein-rich domains,a proline-rich region and a pleckstrin homology domain with overlapping ras-associating domain." J.Biol.Chem.272. 10422-10428 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sakisaka,T., et al.: "Phosphatidylinositol 4,5-bisphosphate phosphatase regulates the rearrangement of actin filaments." Mol.Cell Biol.17. 6246-6253 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Matuoka,K., et al.: "Phosphatidylinositol 4,5-bisphosphate phosphatase regulates the rearrangement of actin filaments." Biochem.Biophys.Res.Commun.239. 488-492 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fukuoka,M., et al.: "dentification of N-WASP homologs in human and rat brain." Gene. 196. 43-48 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Miki,H., et al.: "N-WASP,not WASP,induces filopodium formation downstream of Cdc42." Nature. 391. 93-96 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Fukami,et al: "Identification of a PIP2 binding site in chicken skeletal muscle α-actinin" J.Biol.Chem.271. 2646-2650 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Moriya,et al: "PDGF activates protein kinase C ε through redundant and indedundant signaling pathway involving phospholipase C γ or phospatidylinositol 3-kmase" Proc.Natl.Acad.Sci.USA. 93. 151-155 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Miura,et al: "Interaction of Ash/Grb2 via its SH3 domains with neuron-specific p150 and p65" Biochem.J.316. 639-645 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] M.Matsuda,et al: "Interaction between the amino-terminal SH3 domain of Crk and its natural target proteins" J.Biol.Chem.271. 14468-14472 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] H.Miki,et al: "A novel actin-depolymerizing protein N-WASP regulates thecor-tical cytoskeletal rearrangement in a PIP2 dependent manner at the downstream of tyrosine kinase" EMBO J.15. 5326-5335 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T.Ito,et al: "β-Tubulin binds Src homorogy 2 domains through a region different from the tyrosinephosphorylated protein-recognizing site" J.Biol.Chem.271. 27931-27935 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] N. Liu, et al.: "A new phospholipase Cδ4 is induced at S-phase of cell cycle and appears in the nucleus" J. Biol. Chem.271. 2646-2650 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] K. Watanabe, et al.: "Splicine isoforms of rat Ash/Grb2P: Isolation and characterization of the cDNA and genomic DNA clones and implications for the physiological roles of the isoforms" J. Biol. Chem.270. 13733-13739 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] H. Hosoya, et al.: "Developmental expression of the neural adhesion molecule F3 in the rat brain" Neuroscience Lett.186. 83-86 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] F. Nakamura, et al.: "Characterization of Gq family G proteins. Glla(G14a)Gl2a(Glla), and Gqa expressed in the baculovirus-insect cell" J. Biol. Chem.270. 6246-6253 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] J. C. Hay, et al.: "ATP-dependent inositide phosphorylation required for Ca^<2+>-activated secretion" Nature. 374. 173-177 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] S.Shimihama, et al.: "Characterization of the association of phospholipase C-δ with Alzheimer neurofibrillary tangles" Brain Research.669. 217-224 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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