Poon, C.L.C., Liu, W., Song, Y., Gomez, M., Kulaberoglu, Y., Zhang, X., Xu, W., Veraksa, A., Hergovich, A., Ghabrial, A., Harvey, K.F. (2018). A Hippo-like Signaling Pathway Controls Tracheal Morphogenesis in Drosophila melanogaster.  Dev. Cell 47(5): 564--575.e5.

FBrf0240713

Research paper

Hippo-like pathways are ancient signaling modules first identified in yeasts. The best-defined metazoan module forms the core of the Hippo pathway, which regulates organ size and cell fate. Hippo-like kinase modules consist of a Sterile 20-like kinase, an NDR kinase, and non-catalytic protein scaffolds. In the Hippo pathway, the upstream kinase Hippo can be activated by another kinase, Tao-1. Here, we delineate a related Hippo-like signaling module that Tao-1 regulates to control tracheal morphogenesis in Drosophila melanogaster. Tao-1 activates the Sterile 20-like kinase GckIII by phosphorylating its activation loop, a mode of regulation that is conserved in humans. Tao-1 and GckIII act upstream of the NDR kinase Tricornered to ensure proper tube formation in trachea. Our study reveals that Tao-1 activates two related kinase modules to control both growth and morphogenesis. The Hippo-like signaling pathway we have delineated has a potential role in the human vascular disease cerebral cavernous malformation.

PMC6281297 (PMC) (EuropePMC)