Mechanisms and roles of spatio-temporal dynamics of SAPKs signaling in determining cell fates.

(1)利用基于荧光蛋白激酶活性传感器的成像分析确定了应激激活蛋白激酶活性的亚细胞分布。(2)我发现SAPKs在细胞质或质膜附近被激活，这取决于施加的应力类型。(3)利用诱导蛋白二聚化系统操纵亚细胞定位的SAPK活性，发现只有在细胞质中持续诱导SAPK活性才能诱导细胞死亡，而诱导瞬时SAPK活性不会导致细胞明显死亡，仅表现为质膜动力学（膜突起和细胞边缘形状）的轻微变化。我们的数据表明，SAPK介导的信号可以决定细胞命运，这取决于细胞内SAPK活性的空间或时间动态。

(1)Subcellular distribution of stress-activated protein kinase activities were determined by imaging analysis using fluorescent protein-based kinase activity sensors. (2) I found SAPKs are activated either in the cytoplasm or near plasma membrane depending on the type of stresses applied. (3)By manipulating subcellular-localized SAPK activity using inducible protein dimerization system, I found that cell death was induced only when sustained SAPK activity was induced in cytoplasm, while induction of transient SAPK activity resulted in no obvious cell death and showed only slight change in plasma membrane dynamics (membrane brebbing and shape of cell edge). Our data suggest that SAPK mediated signal can determine cell fates depending on the spatial or temporal dynamics of SAPK activity inside cells.