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Research for a protein tyrosine phosphatase for cell adhesion and its mutations in gastrointestinal cancers.

Research Project

Project/Area Number 09670549
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionKobe University

Principal Investigator

MATOZAKI Takashi  Kobe University School of Medicine, Assistant professor, 医学部・附属病院, 助手 (80252782)

Co-Investigator(Kenkyū-buntansha) AOYAMA Nobuo  Kobe University School of Medicine, Assocaite Professor, 医学部・附属病院, 助教授 (30243299)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsProtein tyrosine phosphatase / PTPH1 / Gastrointestinal cancer / Cell adhesion / PTPH1 / Ezrin
Research Abstract

Since the level of tyrosine phosphorylation is determined by the balance between the actions of both protein tyrosine kinases and protein tyrosine phosphatases (PTPases), not only the unregulated activation of PTKs but also the inactivation of PTPases may be involved in the malignant transformation of gastrointestinal cells. PTPH1 is a human non-transmembrane-type PTPase that has recently been molecularly cloned. This enzyme contains an Ezrin-like structure and a PDZ domain in its N-terminal region. Since Ezrin-like structures are suggested to be involved in cell adhesion, PTPH1 may locate at the cell adhesion sites and regulate cell adhesion through the control of tyrosine phosphorylation of proteins at cell adhesion sites. In this study, we investigated the physiological roles of PTPH1 and clinical applications of PTPH1. (1) PTPH1 located at cell adhesion sites. (2) Transfection of PTPH1 mutants into cultured cells did not show any changes in terms of cell adhesion. We will further examine the effect of microinjection of antibody to PTPH1 into cultured cells. (3) With the use of RT-P CR, we have examined the mutations of PTPH1 gene in various gastrointestinal cancers. We have found several mutations in PTPH1 gene in gastrointestinal cancer sample. We will further investigate whether the mutations found in gastrointestinal cancers results in oncogenesis of these cancers. In addition, we will try to identify the proteins bound to the Ezrin domain or the PDZ domain of PTPH1 by the yeast two-hybrid system.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Takada,T.: "Roles of the complex formation of SHPS-1 with SHLP-2 in insulin-stimulated MAP kinase activation." J.Biol.Chem.273・15. 9234-9242 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsuda,M.: "Integrin-mediated tyrosine phosphorylation of SHPS-1. and its association with SHP-2:Roles of FAK and SRC family kinases." J.Biol.Chem.273・21. 13223-13229 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeda,H.: "Lysophosphatidic acid-induced association of SHP-2 with SHPS-1:Roles of RHO,FAK,and a SRC family kinase." Oncogene. 16・23. 3019-3028 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ogawa,W.: "Role of binding proteins to IRS-1 in insulin signalling." Mol.Cell.Biochem.182・1-2. 13-22 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kuroda, N.: "Differential expression of SHP2,a protein-tyrosine phosphatase with SRC homology-2 domins,in various types of renal tumor." Virchows Arch.433・4. 331-339 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeda,H.: "PI 3-kinase γ and protein kinase C-ζ mediate RAS-independent activation of MAP kinase by a Gi protein-coupled receptor." EMBO J.18・2. 386-395 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takada, T.: "Roles of the complex formation of SHPS-1 with SHP-2 in insulin-stimulated MAP kinase activation." J.Biol.Chem.273. 9234-9242 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsuda, M.: "Integrin-mediated tyrosine phosphorylation of SHPS-1 and its association with SHP-2 : Roles of FAK and SRC family kinases." J.Biol.Chem.273. 13223-13229 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeda, H.: "Lysophosphatidic acid-induced association of SHP-2 with SHPS-1 : Roles of RHO,FAK,and SRC family kinase." Oncogene. 16. 3019-3028 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ogawa, W.: "Roles of binding proteins to IRS-1 in insulin signalling." Mol.Cell.Biochem.182. 13-22 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kuroda, N.: "Differential expression of SHP2, a protein-tyrosine phosphatase with SRC homology-2 domains, in various types of renal tumors." Virchows Arch.433. 331-339 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeda, H.: "PI 3-kinase gamma and protein kinase C-zeta mediate RAS-independent activation of MAP kinase by a Gi protein-coupled receptor." EMBO J.18. 386-395 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takada,T.: "Roles of the complex formation of SHPS-1 with SHP-2 in insulin-stimulated MAP kinase activation." J.Biol.Chem.273・15. 9234-9242 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tsuda,M.: "Inteqrin-mediated tyrosine phosphorylation of SHPS-1 and its association with SHP-2 : Roles of FAK and SRC family kinases." J.Biol.Chem.273・21. 13223-13229 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takeda,H.: "Lysophosphatidic acid-induced association of SHP-2 with SHPS-1 : Roles of RHO, FAK, and a SRC family kinase." Oncogene. 16・23. 3019-3028 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ogawa,W.: "Role of binding proteins to IRS-1 in insulin signalling." Mol.Cell.Biochem.182・1-2. 13-22 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kuroda,N.: "Differential expression of SHP2, a protein-tyrosine Phosphatase with SRC homology-2 domins, in various types of renal tumor." Virchows Arch.433・4. 331-339 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takeda,H.: "PI 3-kinase γ and protein kinase C-ζ mediate RAS-independent activation of MAP kinase by a Gi protein-coupled receptor." EMBO J.18・2. 386-395 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tsuda,M et al.: "Integrin-mediated tyrosine phosphorylation of SHPS-1" J.Biol.Chem.(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takada,T.et al.: "Poles of complex formation of SHPS-1 with SHP-2" J.Biol.Chem.(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takeda,H.et al.: "Lycophosphatidic acid-induced association of SHP-2" Oncogene. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Seo,Y.et al.: "Orerexpression of SAP-1,a transmembrane-type" Biochem.Biophys.Rcs.Commun.231. 705-711 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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