A STAT-regulated, stress-induced signalling pathway in Dictyostelium
A STAT-regulated, stress-induced signalling pathway in Dictyostelium
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DOI：
10.1242/jcs.00501
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发表时间：
2003-07-15
影响因子：
4
通讯作者：
Williams, JG
中科院分区：
文献类型：
--
作者：
Araki, T;Tsujioka, M;Williams, JG
盘基网柄菌茎细胞诱导分化诱导因子 (DIF) 指导酪氨酸磷酸化和 STAT（信号转导器和转录激活剂）蛋白 Dd-STATc 的核积累。我们发现高渗应激、热休克和氧化应激也会激活 Dd-STATc。众所周知，高渗应激会提高细胞内 cGMP 和 cAMP 水平，而膜渗透类似物 8-溴-cGMP 会迅速激活 Dd-STATc，而 8-溴-cAMP 的诱导剂效果要差得多。然而，令人惊讶的是，Dd-STATc 在已知 cGMP 介导和 cAMP 介导的应激反应途径的无效突变体中以及在影响这两种途径的双突变体中仍然是应激可激活的。此外，Dd-STATc 缺失细胞对高渗应激并不异常敏感。微阵列分析鉴定出两个基因，gapA 和 rtoA，是由高渗应激诱导的。 gapA 和 rtoA 的渗透胁迫诱导完全依赖于 Dd-STATc。这两个基因都不能被 DIF 诱导，但都可以被 8-bromo-cGMP 快速诱导。同样，8-溴-cAMP 是比 8-溴-cGMP 效力低得多的诱导剂。这些数据表明，Dd-STATc 在应激反应途径中充当转录激活剂，并且药理学证据至少与 cGMP 作为第二信使的作用一致。
The Dictyostelium stalk cell inducer differentiation-inducing factor (DIF) directs tyrosine phosphorylation and nuclear accumulation of the STAT (signal transducer and activator of transcription) protein Dd-STATc. We show that hyperosmotic stress, heat shock and oxidative stress also activate Dd-STATc. Hyperosmotic stress is known to elevate intracellular cGMP and cAMP levels, and the membrane-permeant analogue 8-bromo-cGMP rapidly activates Dd-STATc, whereas 8-bromo-cAMP is a much less effective inducer. Surprisingly, however, Dd-STATc remains stress activatable in null mutants for components of the known cGMP-mediated and cAMP-mediated stress-response pathways and in a double mutant affecting both pathways. Also, Dd-STATc null cells are not abnormally sensitive to hyperosmotic stress. Microarray analysis identified two genes, gapA and rtoA, that are induced by hyperosmotic stress. Osmotic stress induction of gapA and rtoA is entirely dependent on Dd-STATc. Neither gene is inducible by DIF but both are rapidly inducible with 8-bromo-cGMP. Again, 8-bromo-cAMP is a much less potent inducer than 8-bromo-cGMP. These data show that Dd-STATc functions as a transcriptional activator in a stress-response pathway and the pharmacological evidence, at least, is consistent with cGMP acting as a second messenger.