Developmental Biology, ZHMB (Center of Human and Molecular Biology), Saarland University, Building 61, D-66421 Homburg, Germany.
Department 8.3 Biosciences, Zoology/Physiology-Neurobiology, ZHMB (Center of Human and Molecular Biology), Saarland University, Building B2.1, D-66123 Saarbrücken, Germany.
Int J Mol Sci. 2021 Feb 13;22(4):1862. doi: 10.3390/ijms22041862.
Developmental growth and patterning are regulated by an interconnected signalling network of several pathways. In , the Warts (Wts) kinase, a component of the Hippo signalling pathway, plays an essential role in regulating transcription and growth by phosphorylating its substrate Yorkie (Yki). The phosphorylation of Yki critically influences its localisation and activity as a transcriptional coactivator. In this study, we identified the homeodomain-interacting protein kinase (Hipk) as another kinase that phosphorylates Yki and mapped several sites of Yki phosphorylated by Hipk, using in vitro analysis: Ser168, Ser169/Ser172 and Ser255. These sites might provide auxiliary input for Yki regulation in vivo, as transgenic flies with mutations in these show prominent phenotypes; Hipk, therefore, represents an additional upstream regulator of Yki that works in concert with Wts.
发育生长和模式形成受到多个信号通路的相互关联的信号网络的调节。在果蝇中，Hippo 信号通路的组成部分 Warts (Wts) 激酶通过磷酸化其底物 Yorkie (Yki) 来发挥调节转录和生长的关键作用。Yki 的磷酸化极大地影响了其作为转录共激活因子的定位和活性。在这项研究中，我们鉴定了同源域相互作用蛋白激酶 (Hipk) 作为另一种磷酸化 Yki 的激酶，并通过体外分析：Ser168、Ser169/Ser172 和 Ser255，映射了 Hipk 磷酸化的 Yki 的几个位点。这些位点可能为 Yki 在体内的调节提供辅助输入，因为这些位点发生突变的转基因果蝇表现出明显的表型；因此，Hipk 是 Yki 的另一个上游调节剂，与 Wts 协同作用。
