Role of Hic-5, a protein localized at focal adhesion, in promoting cellular senescence in the stress-responses by cells.
| Project/Area Number |
11680704
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cell biology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
ISHINO Masaho Cancer Research Institute, Sapporo Medical University, 附属がん研究所, 講師 (30232325)
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| Co-Investigator(Kenkyū-buntansha) |
SASAKI Terukatsu Cancer Research Institute, Sapporo Medical University, 附属がん研究所, 教授 (00045494)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| 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)
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| Keywords | intracellular signal transduction / tyrosine phosphorylation / stress response / Hic-5 / cellular senescence / チロシンリン酸化 |
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| 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
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Research Products
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