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2001 Fiscal Year Final Research Report Summary

Protein-protein interaction in intracellular signal transduction

Research Project

Project/Area Number 10179104
Research Category

Grant-in-Aid for Scientific Research on Priority Areas (A)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionHokkaido University (1999-2001)
Tokyo Metropolitan Organization for Medical Research (1998)

Principal Investigator

INAGAKI Fuyuhiko  Hokkaido University, professor, 大学院・薬学研究科, 教授 (70011757)

Co-Investigator(Kenkyū-buntansha) TSUKITA Shoichiro  Kyoto University, professor, 大学院・医学研究科, 教授 (50155347)
YAMAMOTO Tadashi  Tokyo University, professor, 医科学研究所, 教授 (40134621)
TAKENAWA Tadaomi  Tokyo University, professor, 医科学研究所, 教授 (40101315)
KOHDA Daisuke  Kyushu University, professor, 生体防御医学研究所・バイオサイエンス研究, 教授 (80186618)
HAKOSHIMA Toshio  Nara Institute of Science and Technology, professor, バイオサイエンス研究科, 教授 (00164773)
Project Period (FY) 1998 – 2001
KeywordsVav / SH3 / Grb2 / praline rich region / tertiary structure IP3 / radixin / IP3 / PTB様ドメイン
Research Abstract

Vav is a guanine nucleotide exchange factor for the Rho/Rac family that is expressed exclusively in hematopoietic cells. Growth factor receptor-bound protein 2 (Grb2) has been proposed to play important roles in the membrane localization and activation of Vav through dimerization of its C-terminal Srchomology 3 (SH3) domain (GrbS) and the N-terminal SH3 domain of Vav (VavS). The crystal strucuture of VavS complexed with GrbS has been solved. VavS is distinct from other SH3 domain proteins in that its binding site for proline-rich peptides is blocked by its own RT loop. One of the ends of the VavS β-barrel forms a concave hydrophobic surface. The GrbS components make a contiguous complementary interface with the VavS surface. The binding site of GrbS for VavS partially overlaps with the canonical binding site for proline-rich peptides, but is definitely different. Mutations at the interface caused a decrease in the binding affinity of VavS for GrbS by 4- to 40-fold. The structure reveals how GrbS discriminates VavS specifically from other signaling molecules without binding to the proline-rich motif.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Ponting, C.P.: "OPR, PC and AID : all in the PB1 family"TIBS. 27. 10 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ogura, K.: "Solution structure of N-terminal SH3 domain of Vav and the recognition site for Grb2 C-terminal SH3 domain"J.Biomol.NMR. 22. 37-46 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawasaki, M.: "Random PCR-Based screening for soluble domains using green fluorescent protein"Biochem.Biophys.Res.Commun.. 280. 842-844 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Terasawa, H.: "Structure and ligand recognition of the PB1 domain : A novel protein Modulebinding to the PC motif"The EMBO J.. 20. 3947-3956 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishida, M.: "Novel recognition mode between Vav and Grb2 SH3 domains"The EMBO J.. 20. 2995-3007 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yuzawa, S: "Solution structure of Grb2 reveals extensive flexibility for target recognition"J.Mol.Biol.. 306. 527-537 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Panting, C. P., Ito, T., Moscat, J., Diaz-Mew, M., Inagaki, F., Sumimoto, H.: "OPR, PC and AID : all in the PB1 femily"TIBS. 27. 10 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ogura, K., Nagata, K., Horiuchi, M., Ebisui, E., Hasuda, T., Yuzawa, S., Nishida, M., Hatanaka, H., Inagaki, F.: "Solution structure of N-terminal SH3 domain of Vav and the recognition site for Grb2 C-terminal SH3 domain"J. Biomal. NMR. 22. 37-46 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Terasawa, H., Noda, Y., Ito, T., Hatanaka, H., Ichikawa, S., Ogura, K., Sumimoto, H., Inagaki, F.: "Structure and ligand recognition of the PBI domain : A novel protein modulebinding to the PC motif"EMBO J., 20. 15. 3947-3956 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishida, M., Nagata, K., Hachimori, Y., Horiuchi, M., Ogura, Mandiyan, K. V., Schlessinger, J., Inagaki, F.: "Novel recognition mode between Vav and Grb2 SH3 domains"EMBO J. 20. 12. 2995-3007 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawasaki, M, Inagaki, F.: "Random PCR-Based screening for soluble domains using green fluorescent protein"Biochem. Biophys. Res. Commun.. 280, 3. 842-844 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yuzawa, S., Yokochi, M., Hatanaka, H., Ogura, K., Kataoka, M., Miura, K., Mandiyan, K. V., Schlessinger, J., Inagaki, F.: "Solution structure of Grb2 reveals extensive flexisibility necessary for recognition"J. Mol. Biol.. 306. 527-537 (2001)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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