Article

Salt-inducible kinases regulate growth through the Hippo signalling pathway in Drosophila.

1] Apoptosis and Proliferation Control Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK [2] Research Group Gene Expression, Max Planck Institute of Experimental Medicine, Hermann-Rein-Straße 3, D-37075 Göttingen, Germany.
Nature Cell Biology (Impact Factor: 20.06). 12/2012; DOI: 10.1038/ncb2658
Source: PubMed

ABSTRACT The specification of tissue size during development involves the coordinated action of many signalling pathways responding to organ-intrinsic signals, such as morphogen gradients, and systemic cues, such as nutrient status. The conserved Hippo (Hpo) pathway, which promotes both cell-cycle exit and apoptosis, is a major determinant of size control. The pathway core is a kinase cassette, comprising the kinases Hpo and Warts (Wts) and the scaffold proteins Salvador (Sav) and Mats, which inactivates the pro-growth transcriptional co-activator Yorkie (Yki). We performed a split-TEV-based genome-wide RNAi screen for modulators of Hpo signalling. We characterize the Drosophila salt-inducible kinases (Sik2 and Sik3) as negative regulators of Hpo signalling. Activated Sik kinases increase Yki target expression and promote tissue overgrowth through phosphorylation of Sav at Ser 413. As Sik kinases have been implicated in nutrient sensing, this suggests a link between the Hpo pathway and systemic growth control.

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