1] Cell Growth and Proliferation Laboratory, Peter MacCallum Cancer Centre, 7 St Andrews Place, East Melbourne, Victoria 3002, Australia [2] Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3010, Australia.
Nat Cell Biol. 2013 Oct;15(10):1176-85. doi: 10.1038/ncb2829. Epub 2013 Aug 18.
The atypical cadherins Fat (Ft) and Dachsous (Ds) control tissue growth through the Salvador-Warts-Hippo (SWH) pathway, and also regulate planar cell polarity and morphogenesis. Ft and Ds engage in reciprocal signalling as both proteins can serve as receptor and ligand for each other. The intracellular domains (ICDs) of Ft and Ds regulate the activity of the key SWH pathway transcriptional co-activator protein Yorkie (Yki). Signalling from the FtICD is well characterized and controls tissue growth by regulating the abundance of the Yki-repressive kinase Warts (Wts). Here we identify two regulators of the Drosophila melanogaster SWH pathway that function downstream of the DsICD: the WD40 repeat protein Riquiqui (Riq) and the DYRK-family kinase Minibrain (Mnb). Ds physically interacts with Riq, which binds to both Mnb and Wts. Riq and Mnb promote Yki-dependent tissue growth by stimulating phosphorylation-dependent inhibition of Wts. Thus, we describe a previously unknown branch of the SWH pathway that controls tissue growth downstream of Ds.
非典型钙黏蛋白 Fat（Ft）和 Dachsous（Ds）通过 Salvador-Warts-Hippo（SWH）途径控制组织生长，还调节平面细胞极性和形态发生。Ft 和 Ds 进行相互信号传递，因为这两种蛋白可以相互作为受体和配体。Ft 和 Ds 的细胞内结构域（ICD）调节关键的 SWH 途径转录共激活蛋白 Yorkie（Yki）的活性。FtICD 的信号传递已得到很好的描述，通过调节 Yki 抑制性激酶 Warts（Wts）的丰度来控制组织生长。在这里，我们确定了两种果蝇 SWH 途径的调节剂，它们在 DsICD 下游发挥作用：WD40 重复蛋白 Riquiqui（Riq）和 DYRK 家族激酶 Minibrain（Mnb）。Ds 与 Riq 发生物理相互作用，Riq 结合 Mnb 和 Wts。Riq 和 Mnb 通过刺激 Wts 的磷酸化依赖性抑制来促进 Yki 依赖性组织生长。因此，我们描述了一个以前未知的 SWH 途径分支，它在 Ds 下游控制组织生长。
