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2002 Fiscal Year Final Research Report Summary

Regulatory mechanisms for the Ras and Rho family GTP ase network

Research Project

Project/Area Number 13680713
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionKobe University

Principal Investigator

SATOH Takaya  Kobe University Graduate School of Medicine, Department of Molecular and Cellular Biology Associate Professor, 大学院・医学系研究科, 助教授 (20251655)

Project Period (FY) 2001 – 2002
KeywordsGEF / Db1ファミリー / GTP結合蛋白質 / Rhoファミリー / Cdc42 / ACK-1 / PLCε
Research Abstract

Regulatory mechanisms of Ras and Rho family GTP-binding proteins by guanine nucleotide exchange factors (GEFs) were explored. First, the role of Dbl in the regulation of the Rho family upon extracellular stimulation was analyzed. Dbl is tyrosine-phosphorylated by ACK-1, a target of Cdc42, and thereby its GEF activity is enhanced. In addition, Dbl forms a complex with the adaptor Grb2 and the epidermal growth factor (EGF) receptor. We showed that, upon EGF stimulation, ACK-1 and Dbl were tyrosine-phosphorylated and activated in a Cdc42 and Grb2-dependent manner, leading to actin cytoskeletal rearrangements through RhoA, Rac1, and Cdc42. Second, the function of the Sec14-like domain at the N-terminus in a set of Dbl and Dbs splice variants was analyzed. When ectopically expressed in HeLa cells, Dbl and Dbs splice variants induced different morphological alterations depending on the Sec14-like domain. The difference may be due to different subcellular localization of active Rho family members determined by the GEFs. Third, we investigated the role the CDC25 homology domain of PLCε. PLCε is a downstream target of Ras and Rap1, containing a CDC25 homology domain, which is responsible for sustained activation downstream of Rap1 in the Golgi apparatus. We demonstrated that platelet-derived growth factor-induced transient activation of PLCε is mediated by Ras, whereas sustained activation is dependent on Rap1.

  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Dongmei Wu: "Neuronal lineage-specific upregulation of phospholipase C_ε expression in the developing mouse brain"Eur.J.Neurosci.. 17. 1571-1580 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yukinori Minoshima: "Phosphorylation of MgcRacGAP by Aurora B kinase leads to induction of its latent GAP activity towards RhoA during mitosis ; identification of a RhoGAP indispensible for the completion of cytokinesis"Dev.Cell. 4. 549-560 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chunhua Song: "Differential roles of Ras and Rapl in growth factro-dependent activation of phospholipase C_ε"Oncogene. 21. 8105-8113 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Xianlong Gao: "Identification and charactarization of RA-GEF-2,a Rap guanine nucleotide exchange factor that serves as a downstream target of M-Ras"J.Biol.Chem.. 276. 42219-42225 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tai-Guang Jin: "Role of the CDC25 homology domain of phospholipase Ce in amplification of Rapl-dependent singaling"J.Biol.Chem.. 276. 30301-30307 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Juran Kato-Stankiewicz: "Epidermal growth factor stimulation of the ACKl/Dbl pathway in a Cdc42 and Grb2-dependent manner"Biochem.Biophys.Res.commun.. 284. 470-477 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chunhua Song, Ghang-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(4). 2752-2757 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Juran Kato-Stankiewicz, Shuji Ueda, Tohru Kataoka, Yoshito Kaziro, and Takaya Satoh: "Epidermal growth factor stimulation of the ACK1/Dbl pathway in a Cdc42 and Grb2-dependent manner"Biochem.Biophys.Res.Commun. 284(2). 470-477 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yanhong Liao, Takaya Satoh, Xianlong Gao, Tai-Guang Jin, Chang-Deng Hu, and Tohru Kataoka: "RA-GEF-1, a guanine nucleotide exchange factor for Rap1, is activated by translocation induced by association with Rap1-GTP and enhances Rap1-dependent B-Raf activation"J.Biol.Chem. 276(30). 28478-28483 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tai-Guang Jin, Takaya Satoh, Yanhong Liao, Chunhua Song, Xianlong Gao, Ken-ichi Kariya, Chang-Deng Hu, and Tohru Kataoka: "Role of the CDC25 homology domain of phospholipase Ce in amplification of Rap1-dependent signaling"J.Biol.Chem. 276(32). 30301-30307 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Xianlong Gao, Takaya Satoh, Yanhong Liao, Chunhua Song, Chang-Deng Hu, Ken-ichi Kariya, and Tohru Kataoka: "Identification and characterization of RA-GEF-2, a Rap guanine nucleotide exchange factor that serves as a downstream target of M-Ras"J.Biol.Chem. 276(45). 42219-42225 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Masahiro Kido, Fumi Shima, Takaya Satoh, Tsuyoshi Asato, Ken-ichi Kariya, and Tohru Kataoka: "Critical function of the Ras-associating domain as a primary Ras-binding site for regulation of Saccharomyces cerevisiae adenylyl cyclase"J.Biol.Chem. 277(5). 3117-3123 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chunhua Song, Takaya Satoh, Hironori Edamatsu, Dongmei Wu, Makoto Tadano, Xianlong Gao, and Tohru Kataoka: "Differential roles of Ras and Rap1 in growth factor-dependent activation of phospholipase Cε"Oncogene. 21(53). 8105-8113 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yukinori Minoshima, Toshiyuki Kawashima, Koichi Hirose, Yukio Tonozuka, Aie Kawajiri Ying Chun Bao, Xingming Deng, Masaaki Tatsuka, Shuh Narumiya, W.Stratford May,Jr., Tetsuya Nosaka, Kentaro Semba, Takafumi Inoue, Takaya Satoh, Masaki Inagaki, and Toshio Kitamura: "Rhosphorylation by Aurora B converts MgcRacGAP to a RhoGAP during cytokinesis"Dev.Cell. 4(4). 549-560 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Dongmei Wu, Makoto Tadano, Hironori Edamatsu, Misa Masago-Toda, Yuriko Yamawaki-Kataoka, Toshio Terashima, Akira Mizoguchi, Yasuhiro Minami, Takaya Satoh, and Tohru Kataoka: "Neuronal lineage-specific induction of phospholipase Ce expression in the developing mouse brain"Eur.J.Neurosci. 17(8). 1571-1580 (2003)

    • 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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