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Role of Hic-5, a protein localized at focal adhesion, in promoting cellular senescence in the stress-responses by cells.

Research Project

Project/Area Number 11680704
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionSapporo Medical University

Principal Investigator

ISHINO Masaho  Cancer Research Institute, Sapporo Medical University, 附属がん研究所, 講師 (30232325)

Co-Investigator(Kenkyū-buntansha) SASAKI Terukatsu  Cancer Research Institute, Sapporo Medical University, 附属がん研究所, 教授 (00045494)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
Keywordsintracellular signal transduction / tyrosine phosphorylation / stress response / Hic-5 / cellular senescence / チロシンリン酸化
Research Abstract

Hic-5 is localized at focal adhesions of fibroblast. This localization suggests a possibility that Hic-5 may mediate cellular signaling in response to the stimulation of integrins and growth factor receptors. It was also reported that Hic-5 translocated into nucleus : these studies implicated a function of Hic-5 in the process of cellular senescence and stress response. We therefore investigated, in order to study function of Hic-5, how the localization of Hic-5 within cells is regulated.
First, we analyzed tyrosine phosphorylation of Hic-5 in stimulated cells to study possible involvement of Hic-5 in signal transduction. Our previous experiments showed that Hic-5 was tyrosine phosphorylated when cells were exposed to hyperosmotic stress. In the present study, we introduced Hic-5 cDNA into COS-7 cells which do not express Hic-5 endogenously. We did not observe tyrosine phoshporylation of Hic-5 even after the exposure of these COS-7 cells to osmotic stress. However, the Hic-5 expressed i … More n COS-7 cells was phosphorylated upon osmotic stress when Fyn and CAK β, but not FAK, was expressed together with Hic-5. Under the conditions in COS-7 cells, Hic-5 was phosphorylated on tyrosine 60. It was shown that the phosphorylation of tyrosine 60 was necessary for the specific binding of Hic-5 to the SH2 domain of Csk. This result implies specific protein-protein interactions of Hic-5 and SH2 proteins, caused by activation of CAKβ and Fyn, leading to downstream signalings.
It was reported that tyrosine phosphorylation of paxillin correlates with protrusion of filopodial structures and an increase in the number of focal adhesions of the cell. We overexpressed Hic-5 in fibroblasts by the use of recombinant adenovirus in an attempt to replace paxillin at focal adhesions with Hic-5. We found that the cell protrusion was indeed affected by Hic-5 expression. Because Hic-5 lacks the SH2 and SH3 binding motifs characteristically found in paxillin, our results suggest that these motifs is probably important in organizing new focal adhesions. Thus, unlike paxillin, phosphorylation of tyrosine 60 of Hic-5 cannot induce the formation of focal adhesion but may activate some other signaling pathway. Less

Report

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

    (16 results)

All Other

All Publications (16 results)

  • [Publications] 佐々木輝捷,青砥宏,佐々木洋子,石埜正穂: "非受容体型蛋白質チロシンキナーゼCAKβ/PYK2"蛋白質核酸酵素. 44. 112-122 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Katagiri T,Takahashi T,Sasaki T,Nakamura S,Hattori S.: "Protein-tyrosine kinase PYK2 is involved in interleukin-2 production by jurkat T cells via its tyrosine 402"Journal of Biological Chemistry. 275. 19645-19652 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishino M,Aoto H,Sasaski H,Suzuki R,and Sasaki T.: "Phosphorylation of Hic-5 at tyrosine 60 by CAKβ and Fyn"FEBS Letters. 474・2-3. 179-183 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Aoto H,Mitaka T,Sasaski H,Ishino M,Mochizuki Y,and Sasaki T.: "Association of cell adhesion kinase beta (CAKβ/PYK2) with cytoskeleton."Tumor Research. 35. 35-47 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishino M,Aoto H,Sasaski H,Muramatsu F,Yamashiro S,Sasaki T.: "Identification of SH3-domain binding proteins from cell and tissue extracts by using peptide-mass fingerprinting."Tumor Research. 35. 57-62 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Katagiri T, Takahashi T, Sasaki T, Nakamura S, Hattori S.: "Proteintyrosine kinase PYK2 is involved in interleukin-2 production by Jurkat T cells via its tyrosine 402."J Biol Chem. 275. 19645-19652 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishino M, Aoto H, Sasaski H, Suzuki R, and Sasaki T.: "Phosphorylation of Hic-5 at tyrosine 60 by CAKβ and Fyn."FEBS Lett. 474. 179-183 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Aoto H, Mitaka T, Sasaski H, Ishino M, Mochizuki Y, and Sasaki T.: "Association ofcell adhesion kinase β (CAK β/PYK2) with cytoskeleton."Tumor Research. 35. 35-47 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishino M, Aoto H, Sasaski H, Muramatsu F, Yamashiro S, Sasaki T.: "Identification of SH3-domain binding proteins from cell and tissue extracts by using peptide-mass fingerprinting."Tumor Research. 35. 57-62 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sasaki T, Aoto H, Sasaki H, Ishino M.: "Non-receptor protein tyrosine kinase CAK β/PYK2."Tanpakushitsu Kakusan Koso. 44. 112-22 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 佐々木輝捷,青砥宏,佐々木洋子,石埜正穂: "非受容体型蛋白質チロシンキナーゼCAKβ/PYK2"蛋白質核酸酵素. 44. 112-122 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Katagiri T,Takahashi T,Sasaki T,Nakamura S,Hattori S.: "Protein-tyrosine kinase PYK2 is involved in interleukin-2 production by Jurkat T cells via its tyrosine 402"Journal of Biological Chemistry. 275. 19645-19652 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ishino M,Aoto H,Sasaski H,Suzuki R,and Sasaki T.: "Phosphorylation of Hic-5 at tyrosine 60 by CAKβ and Fyn"FEBS Letters. 474・2-3. 179-183 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Aoto H,Mitaka T,Sasaski H,Ishino M,Mochizuki Y,and Sasaki T.: "Association ofcell adhesion kinase beta(CAKβ/PYK2)with cytoskeleton."Tumor Research. 35. 35-47 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ishino M,Aoto H,Sasaski H,Muramatsu F,Yamashiro S,Sasaki T.: "Identification of SH3-domain binding proteins from cell and tissue extracts by using peptide-mass fingerprinting."Tumor Research. 35. 57-62 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 佐々木輝捷,青砥宏,佐々木洋子,石埜正穂: "非受容体蛋白質チロシンキナーゼCAKβ/PYKα"蛋白質・核酸・酵素. 44・2. 112-122 (1999)

    • Related Report
      1999 Annual Research Report

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

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