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Analysis of signal transduction mediated by Ras and Rac family GTPases

Research Project

Project/Area Number 11680625
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionKobe University (2000)
Tokyo Institute of Technology (1999)

Principal Investigator

SATO Takaya  (Associate Professor, Kobe University School of Medicine), 医学部, 助教授 (20251655)

Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsGEF / Dbl / ACK-1 / Rho / Cdc42 / Ras-GRF-1 / Src / Ras / Ras-GRF1 / ACK / Rac
Research Abstract

The role of guanine nucleotide exchange factors (GEFs) for Ras and Rho family GTP-binding proteins was explored. Dbl is a prototype of Dbl family GEFs, containing tandem DH and PH domains, which are responsible for GEF activity toward Rho family GTP-binding proteins. G protein βγ subunits (Gβγ) bind to the N-terminal region of Dbl although the role in the regulation of GEF activity remains elusive. Furthermore, the tyrosine kinase ACK-1, an effector of Cdc42, phosphorylates Dbl thereby stimulating GEF activity. In fact, the epidermal growth factor receptor activates ACK-1 in a Grb-2 and Cdc42-dependent manner, which in turn phosphorylates Dbl, leading to actin cytoskeletal reorganization. Ras-GRF-1 was originally isolated as a Ras GEF that is expressed exclusively in the brain. We found that the Gβγ signal induced GEF activity of Ras-GRF-1 toward Rac that is latent without stimulation. As expected, DH and PH domains were required for this activity. Gβγ-dependent tyrosine phosphorylation of Ras-GRF-1 was critical for the induction of GEF activity toward Rac. The non-receptor tyrosine kinase Src phosphorylates Ras-GRF-1, and induces its Rac GEF activity in vivo and in vitro. Thus, Src may be involved in Gβγ-dependent activation of Ras-GRF-1. On the other hand, ACK-1 as well stimulates tyrosine phosphorylation of Ras-GRF-1, thereby enhancing GEF activity toward Ras.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Mari Kiyono: "G protein βγsubunit-dependent Rac-guanine nucleotide exchange activity of Ras-GRF1/CDC25^<Mm>."Proc.Natl.Acad.Sci.USA. 96. 4826-4831 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kazuhiko Nishida: "Association of the proto-oncogene product Dbl with G protein βγsubunits."FEBS Lett.. 459. 186-190 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Juran Kato: "Activation of the guanine nucleotide exchange factor Dbl following ACK1-dependent tyrosine phosphorylation."Biochem.Biophys.Res.Commun.. 268. 141-147 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mari Kiyono: "Induction of Rac-guanine nucleotide exchange activity of Ras-GRF1/CDC25^<Mm> following phosphorylation by the nonreceptor tyrosine kinase Src."J.Biol.Chem.. 275. 5441-5446 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mari Kiyono: "Stimulation of Ras guanine nucleotide exchange activity of Ras-GRF1/CDC25^<Mm> upon tyrosine phosphorylation by the Cdc42-regulated kinase ACK1."J.Biol.Chem.. 275. 29788-29793 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Chunhua Song: "Regulation of a novel human phospholipase C,PLC_ε,through membrane targeting by Ras."J.Biol.Chem.. 276. 2752-2757 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mari Kiyono, Takaya Satoh, and Yoshito Kaziro: "G protein βγ subunit-dependent Rac-guanine nucleotide exchange activity of Ras-GRF1/CDC25^<Mm>"Proc.Nail.Acad.Sci.USA.. 96. 4826-4831 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kazuhiko Nishida, Yoshito Kaziro, and Takaya Satoh: "Association of the proto-oncogene product Dbl with G protein βγ subunits."FEBS Lett.. 459. 186-190 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Juran Kato, Yoshito Kaziro, and Takaya Satoh: "Activation of the guanine nucleotide exchange factor Dbl following ACK1-dependent tyrosine phosphorylation"Biochem.Biophys.Res.Commun.. 268. 141-147 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mari Kiyono, Yoshito Kaziro, and Takaya Satoh: "Induction of Rac-guanine nucleotide exchange activity of Ras-GRF1/CDC25^<Mm> following phosphorylation by the nonreceptor tyrosine kinase Src."J.Biol.Chem.. 275. 5441-5446 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mari Kiyono, Juran Kato, Tohru Kataoka, Yoshito Kaziro, and Takaya Satoh: "Stimulation of Ras guanine nucleotide exchange activity of Ras-GRF1/CDC25^<Mm> upon tyrosine phosphorylation by the Cdc42-regulated kinase ACK1."J.Biol.Chem. 275. 29788-29793 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Chunhua Song, Chang-Deng Hu, Misa Masago, Ken-ichi Kariya, Yuriko Yamawaki-Kataoka, Mitsushige Shibatohge Dongmei Wu, Takaya Satoh, and Tohru Kataoka: "Regulation of a novel human phospholipase C,PLCε, through membrane targeting by Ras."J.Biol.Chem.. 276. 2752-2757 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Koji Terada: "Analysis of Ras-dependent signals that prevent caspase-3 activation and apoptosis induced by cytokine deprivation in hematopoietic cells."Biochem.Biophys.Res.Commun.. 267. 449-455 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Juran Kato: "Activation of the guanine nucleotide exchange factor Dbl following ACK1-dependent tyrosine phosphorylation."Biochem.Biophys.Res.Commun.. 268. 141-147 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mari Kiyono: "Induction of Rac-guanine nucleotide exchange activity of Ras-GRF1/CDC25^<Mm> following phosphorylation by the nonreceptor tyrosine kinase Src."J.Biol.Chem.. 275. 5441-5446 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Toshiyuki Kawashima: "MgcRacGAP is involved in the control of growth and differentiation of hematopoietic cells."Blood. 96. 2116-2124 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mari Kiyono: "Stimulation of Ras guanine nucleotide exchange activity of Ras-GRF1/CDC25^<Mm> upon tyrosine phosphorylation by the Cdc42-regulated kinase ACK1."J.Biol.Chem.. 275. 29788-29793 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Chunhua Song: "Regulation of a novel human phospholipase C, PLCε, through membrane targeting by Ras."J.Biol.Chem.. 276. 2752-2757 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kazuhiko Nishida,Yoshito Kuziro Takaya Satoh: "Anti-apoptotic tunction of Rac in hematopoietic cells"Oncogene. 18. 407-415 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Mari Kiyono,Takaya Satoh,Yoshito Kuziro: "G protein βγ subunit-dependent Rac-guanine nncleotide exchange activity of Ras-GRF1/CDC25Mm"Proc.Natl.Acad.Sci.USA. 96. 4826-4831 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kazuhiko Nishida,Yoshito Kuziro Takaya Satoh: "Asseciation of the proto-oncogene product Dbl with G protein βγSubunits"FEBS Lett.. 459. 186-190 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Koji Terada,Yoshito Kaziro, Takaya Satoh: "Analysis of Ras-dependent Signals that prevent caspase-3 activation and apoptosis induced by cylokine deprivaslion in hemastopoietic cells"Biochem.Biophys.Res.Commnun.. 267. 449-455 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Juran Kato,Yoshito Kaziro, Takaya Satoh: "Activation of the guanine uncleotide exchange factor Dbl following ACKI-dependent tyrosine phosphorylation"Biochem.Boiophys.Res.Commun.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Mari Kiyono,Yoshito Kaziro,Takaya Satoh: "Induction of Rac-gnanine nncleotide exchange activity of Ras-GRF1/CDC25Mm following phosphorylation by the nonreceptor tyvozine kinare Src"J.Biol.Chem.. (in press). (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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