Department of Molecular Biology and Biochemistry, Centre for Cell Biology, Development and Disease, Simon Fraser University, Burnaby, B.C Canada.
PLoS One. 2019 Dec 31;14(12):e0226856. doi: 10.1371/journal.pone.0226856. eCollection 2019.
Drosophila has been instrumental as a model system in studying signal transduction and revealing molecular functions in development and human diseases. A point mutation in the Drosophila Janus kinase JAK (called hop) causes constitutive activation of the JAK/STAT pathway. We provide robust genetic evidence that the Homeodomain interacting protein kinase (Hipk) is required for endogenous JAK/STAT activity. Overexpression of Hipk can phenocopy the effects of overactive JAK/STAT mutations and lead to melanized tumors, and loss of Hipk can suppress the effects of hyperactive JAK/STAT. Further, the loss of the pathway effector Stat92E can suppress Hipk induced overgrowth. Interaction studies show that Hipk can physically interact with Stat92E and regulate Stat92E subcellular localization. Together our results show that Hipk is a novel factor required for effective JAK/STAT signaling.
果蝇作为一种模型系统在研究信号转导以及揭示发育和人类疾病中的分子功能方面发挥了重要作用。果蝇 Janus 激酶 JAK（称为 hop）中的一个点突变导致 JAK/STAT 途径的组成性激活。我们提供了强有力的遗传证据表明，同源域相互作用蛋白激酶（Hipk）是内源性 JAK/STAT 活性所必需的。Hipk 的过表达可以模拟过度活跃的 JAK/STAT 突变的效应，并导致黑色素瘤肿瘤，而 Hipk 的缺失可以抑制过度活跃的 JAK/STAT 的效应。此外，通路效应物 Stat92E 的缺失可以抑制 Hipk 诱导的过度生长。相互作用研究表明，Hipk 可以与 Stat92E 物理相互作用并调节 Stat92E 的亚细胞定位。我们的研究结果表明，Hipk 是 JAK/STAT 信号有效传递所必需的一种新型因子。
