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Signaling Pathways for Cell Cycle & Growth

Research Project

Project/Area Number 10044261
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionNagoya University

Principal Investigator

HAMAGUCHI Michiaki  Nagoya University, School of Medicine, Professor, 医学部, 教授 (90135351)

Co-Investigator(Kenkyū-buntansha) MATSDA Satoru  School of Medicine, Assistant Professor, 医学部, 講師 (50242110)
HANAFUSA Hidesaburo  Osaka Bio Inst., Director, 所長
MAYER Bruce  ハーバード大学, 医学部, 講師
PELLMAN Davi  ハーバード大学, 医学部, 講師
DUTTA Anyndi  ハーバード大学, 医学部, 講師
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1998: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordscell growth / cell cycle / tyrosine kinase / growth regulator / cell adhesion / 増殖抑制因子
Research Abstract

The aim of this study is to clarify signaling pathway for the regulation of cell cycle that depends on protein-protein interactions regulated by SH2-phosphotyrosine binding or SH3-proline bindings, under the international collaborative study. Advance of recent study revealed that cell growth cycle is regulated by a variety of intracellular signaling pathway that activated by tyrosine phosphorylation of cellular proteins. Up to date, two types of signaling pathway, positive and negative ones, that regulate cell growth were identified.
In this study we mainly focused on a transmembrane glycoprotein, SHPS-1. SHPS-1 appears to have a function as a docking protein that reclutes the tyrosine phosphatase, SHP-2 which seems to be required for the cell growth. Despite for its unique structure, however, the function of SHPS-1 in cell growth remains largely unclear. in this study, we showed that cell transformation by v-src substantially suppresses the expression of SHPS-1 protein. In contrast, overexpression of exogenous SHIPS-1 in v-src-transformed cells virtually suppresses anchorage-independent growth of the cells.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (40 results)

All Other

All Publications (40 results)

  • [Publications] Serbulea, M., Hamaguchi, M. et al.: "Hyaluronan activates mitogen-activated protein kinase via Ras-signaling pathway". Int. J. Oncogene. 14. 733-738 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Akhand, A. A., Hamaguchi, M. et al.: "Nitric oxide controls Src kinase activity through a redox-based molecular modification"J. Biol. Chem.. 274. 25821-25826 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Thant, A. A., Hamaguchi, M.: "Ras pathway is required for the activation of MMP-2 and for the invasion of src-transformed 3Y1"Oncogene. 18(47). 6555-6563 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Itano, N., Hamaguchi., et al.: "Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties"J. Biol. Chem.. 274. 25085-25092 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Miyazaki, K., Hamaguchi, M.: "Critical amino acid substitutions in the Src SH3 domain that convert c-Src to be oncogenic"Biochem. Bioph. Res. Co.. 263. 759-764 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okuda, T., Hamaguchi, M., et al.: "Molecular cloning of macrophin, a human homologue of Drosophila kakapo with a close structural similarity to plectin and dystrophin"Biochem. Bioph. Res. Co.. 264. 568-574 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kurata, K., Hamaguchi, M.: "Constitutive activation of MAP kinase kinsae (MEK1) is critical and sufficient for the activation of MMP-2"Exp. Cell Res.. 254. 180-188 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Senga, T., Hamaguchi, M.: "Clustered cysteine residues in the kinase domain of v-Src : critical role for protein stability, cell transformation and sensitivity to herbimycin A"Oncogene. 19. 273-279 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsuda, S., Hamaguchi, M.: "Molecular cloning and characterization of a novel human gene (HERNA) which encodes a putative RNA-helicase"Biochim. Biophys. Acta. 1490. 163-169 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsuda, S., Hamaguchi, M.: "Molecular cloning and characterization of human MAWD, a novel protein containing WD-40 repeats frequently overexpressed in breast cancer"Cancer Res.. 60. 13-17 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Machida, K., Hamaguchi, M.: "v-Src suppresses SHPS-1 expression via the Ras-MAP kinase pathway to promote the oncogenic growth of cells"Oncogene. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Serbulea, M., Hamaguchi, M. et al.: "Hyaluronan activates mitogen-activated protein kinase via Ras-signaling pathway"Int. J. Onc.. 14. 733-738 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Arkhand, A.A., Hamaguchi, M et al.: "Nitoric oxide controls Src kinase activity through a redox-based molecular modification"J. Biol. Chem.. 274. 25821-25826 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Thant, A. A., Hamaguchi, M.: "Ras pathway is required for the activation of MMP-2 and for the invasion of src-transformed 3Y1"Oncogen. 18(47). 6555-6563 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Itano, N., Hamaguchi, M. et al.: "Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties"J. Biol. Chem. 274. 25085-25092 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Miyazaki, K., Hamaguchi., M. et al.: "Critical amino acid substitutions in the Src SH3 domain that convert C-Src to be oncogenic"Biochem . Bioph. Res. Co.. 263. 759-764 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okuda, T., Hamaguchi., M. et al.: "Molecular cloning of macrophin, a human homologue of Drosophia kakapo whith a close structural similarity to plectin and dystrophin"Biochem . Bioph. Res. Co.. 264. 568-574 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kurata, K., Hamaguchi., M.: "Constitutive activation of MAP kinase kinsae (MEK1) is critical and sufficient for the activation of MMP-2"Exp. Cell. Res.. 254. 180-188 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Senga, T., Hamaguchi, M. et al.: "Clustered cysteine residues in the kinase domain of v-Src : critical role for protein stability, cell transformation and sensitivity to herbimycin A."Oncogene. 19. 273-279 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mastuda, S., Hamaguchi, M. et al.: "Molecular cloning and characterization of a novel human gene (HERNA) which encodes a putatibe RNA-helicase"Biochem. Biophys. Acta. 1490. 163-169 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsuda, S., Hamaguchi. M., et al.: "Molecular cloning and characterization of a human MAWD, a novel protein containing WD-40 repeats frequently overexpressed in breast cancer"Cancer Res.. 60. 13-17 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Machida, K., Hamaguchi, M., et al.: "v-Src suppresses SHPS-1 expression via the Ras-MAP kinase pathway to promote the oncogenic growth of cells"Oncogene. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Serbulea,M.,Hamaguchi,M.et al.: "Hyaluronan activates mitogen-activated protein kinase via Ras-signaling pathway."Int.J.Oncogene. 14. 733-738 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Akhand,A.A.,Hamaguchi,M.et al.: "Nitric oxide controls Src kinase activity through a redox-based molecular modification."J.Biol.Chem.. 274. 25821-25826 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Thant,A.A.,Hamaguchi,M.: "Ras pathway is required for the activation of MMP-2 and for the invasion of src-transformed 3Y1."Oncogene. 18(47). 6555-6563 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Itano,N.,Hamaguchi,,et al.: "Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties."J.Biol.Chem.. 274. 25085-25092 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Miyazaki,K.,Hamaguchi,M.: "Critical amino acid substitutions in the Src SH3 domain that convert c-Src to be oncogenic."Biochem.Bioph.Res.Co.. 263. 759-764 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okuda,T.,Hamaguchi,M.et al.: "Molecular cloning of macrophin,a human homologue of Drosophila kakapo with a close structural similarity to plectin and dystrophin."Biochem.Bioph.Res.Co.. 264. 568-574 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kurata,K.,Hamaguchi,M.: "Constitutive activation of MAP kinase (MEK1) is critical and sufficient for the activation of MMP-2."Exp.Cell.Res.. 254. 180-188 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Senga,T.,Hamaguchi,M.: "Clustered cysteine residues in the kinase domain of v-Src: critical role for protein stability, cell transformation and sensitivity to herbimycin A."Oncogene. 19. 273-279 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Matsuda,S.,Hamaguchi,M.: "Molecular cloning and characterization of a novel human gene (HERNA) which encodes a putative RNA-helicase."Biochim.Biophys.Acta. 1490. 163-169 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Matsuda,S.,Hamaguchi,M.: "Molecular cloning and characterization of human MAWD,a novel protein containing WD-40 repeats frequently overexpressed in breast cancer."Cancer.Res.. 60. 13-17 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Machida,K.,Hamaguchi,M.: "v-Src suppresses SHPS-1 expression via the Ras-MAP kinase pathway to promote the oncogenic growth of cells."Oncogene. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Shibata.K.,Thant,A.A.Hamaguchi,M.et al.: "Both focal adhesion kinase and c-Ras are required for the enhanced Matrix Metalloproteinase-9(MMP-9)secretion by fibronectim in the ovarian cancer cells" CANCER RES.,. 58. 900-903 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Towatari,M.,Kanei,Y.,Hamaguchi,M.et al.: "Hematopoietic transcription factor GATA-2 activates traanscription from HIV-1 long terminal repeat" AIDS. 12. 253-259 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Wang,X.,Thant,A.A.Hamaguchi,M.et al.: "Suppression of cell growth by ectopic expression of N-cadherin." INT.J.ONC.,. 12. 1097-11* (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Naruse.K.,Hamaguchi,M.Sogabe,M.et al.: "Strech dependent tyroshine phosphorylation regulates morphological response of endothelial cells." ONCOGENE. 17. 455-463 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Isogai,C.,Murate,T.,Hamaguchi,M.et al(11): "Sphingosine induced apoptosis in human eukemia cell line,TF1 nad its bc12 transfectant." EXPT.HEMATO.,. 26. 1118-1125 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kuno,Y.,Kondo,K.,Hamaguchi,M.et al(8): "Tumor-specificactivation of mitogen activated protein kinase in human colorectal and gastric carcinoma tissues." JPN.J.CANCER RES.,. 89. 903-909 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kiyoi,H.,Hamaguchi,M.Naoe,T.et al.(6): "Internal tandem duplication of the FLT3 gene is a novel modality of elongation mutation which causes constitutive actvation of the production" LEUKEMIA. 12. 1333-1337 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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