Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Outline of Final Research Achievements |
Quantitative analysis of stress-activated MAPK signaling in cultured cells were done using FRET based sensors. I found that inflammatory cytokines induces oscillatory p38 activation in cytoplasm, and demonstrated that such p38 activation occurs heterogeneously in cells. Gene expression analysis further revealed that oscillatory p38 activities efficiently induces expression of pro-inflammatory cytokine gene expression than continuously elevated p38 activity does. When p38 activity was introduced in cells by inducible rapamycin-dependent dimerization of FRB domain and FKBP-p38 fusion protein, we found that there is some relationship beteween p38 activity and bleb-like plasma-membrane structure even in the absence of upstream signal activation. Such membrane structure was also seen when cells were stimulated by UV stresses or by applying pro-inflammatory cytokines. Thus, this study revealed unexpected p38 signal dynamics as well as its role in inflammatory signaling.
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