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1995 Fiscal Year Final Research Report Summary

Determination of signal transduction pathways involving Ash/Grb2, the adaptor molecule composed of the Src homology regions

Research Project

Project/Area Number 06680706
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Cell biology
Research InstitutionTokyo Metropolitan Institute of Gerontology

Principal Investigator

MATUOKA Koozi  Tokyo Metropolitan Institute of Gerontology Department of Biosignal Research Research Scientist, 生体情報部門, 研究員 (60110029)

Project Period (FY) 1994 – 1995
KeywordsSignal transduction / Src homology / Ash / Grb2 / SH2 / SH3 / Ras / Small GTP-binding protein
Research Abstract

We and another group recently discovered an adaptor protein Grb2/Ash.Here we investigated intramolecular interactions involving Ash to find the following : Ash plays a role in the insulin induction of membrane ruffling ; By its SH2 domain Ash binds directly to the EGF receptor but not to the NGF receptor upon stimulation ; Ash exhibits differential binding to the phosphorylated tyrosines of the EGF receptor (directly to Y 1068 and Y 1086 and indirectly to tyrosine 1148 via Shc) ; Ash binds by its SH3 domains to a variety of signaling molecules, including dynamin, C3G,N-WASP and synaptojanin ; a cDNA library screening resulted in discovery of splicing isomers of Ash, those exhibiting a different binding specificity to the above Ash target molecules.The results show that Ash is a multifunctional signal transducer down from the receptor protein tyrosine kinases.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Watanabe, K.: "Splicing isoforms of rat Ash/Grb2 : Isolation and characterization" J. Biol. Chem.270. 13733-13739 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohmichi, M.: "Growth factors differentially Stimulate the phosphorylation of Shc proteins and their association with Grb2 in PC-12 pheochromocytoma cells" J. Biol. Chem.269. 1143-1148 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hashimoto, Y.: "Different interactions of Grb2/Ash molecule with the NGF and EGF receptors in rat pheochromocytoma PC12 cells" Oncogene. 9. 869-875 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miki, H.: "Association of Ash/Grb2 with dyrawin through the SH3 domain" J. Biol. Chem.269. 5489-5492 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka, S.: "C3G, a guanine nucleotide releasing protein exspressed ubiquitously, binds to the SH3 dowaius of CRK and GRB2/ASH" Proc. Natl. Acad, Sci. USA. 91. 3443-3447 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okutani, T.: "Grb2/Ash binds directty to tyrosines 1068 and 1086 and indirectly to tyrosine 1148 of activated human epidermel growth factor receptors in intact cells" J. Biol. Chem.269. 31310-31314 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanabe K.et al.: "Splicing isoforms of rat Ash/Grb2 : Isolation and chracterization of the cDNA and genomic DNA clones." J.Biol.Chem.270. 13733-13739 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohmichi, M.et al.: "Growth factors differentially stimulate the phosphorylation of Shc proteins and their association with Grb2 in PC-12 pheochromocytoma cells." J.Biol.Chem.269. 1143-1148 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hashimoto, Y.et al.: "Different interactions of Grb2/Ash molecule with the NGF and EGF receptors in rat pheochromocytoma PC12 cells" Oncogene. 9. 869-875 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka, S.et al.: "C3G,a guanine nucleotide releasing protein expressed ubiquitously, binds to the SH3 domains of CRK and GRB2/ASH" Proc.Natl.Acad.Sci.USA. 91. 3443-3447 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miki, H.et al.: "Association of Ash/Grb-2 with dynamin through the SH3 domain." J.Biol.Chem.269. 5489-5492 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okutani, T.et al.: "Grb2/Ash binds directly to tyrosines 1068 and 1086 and indirectly to tyrosine 1148 of activated human epidermal growth factor receptors in intact cells." J.Biol.Chem.269. 31310-31314 (1994)

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

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Published: 1997-03-04  

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