Salt-inducible kinases regulate growth through the Hippo signalling pathway in Drosophila
| Autor: | Maxine V. Holder, Moritz J. Rossner, Ming Jiang, Ieva Gailite, Tobias M. Maile, Elena Ciirdaeva, Michael C. Wehr, Rachael Instrell, Michael Howell, Rebecca E. Saunders, Nicolas Tapon |
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| Rok vydání: | 2012 |
| Předmět: |
endocrine system
animal structures Hpo signalling proliferation Cell Cycle Proteins Protein Serine-Threonine Kinases Biology Article Cell Line Protein Interaction Mapping Animals Drosophila Proteins Wings Animal Phosphorylation Sik3 Sik2 Hippo signaling pathway Protein-Serine-Threonine Kinases split TEV Kinase fungi Intracellular Signaling Peptides and Proteins Nuclear Proteins AMPK YAP-Signaling Proteins Organ Size Cell Biology Hedgehog signaling pathway Cell biology body regions Drosophila melanogaster 14-3-3 Proteins Gene Expression Regulation Gene Knockdown Techniques Trans-Activators RNAi screening RNA Interference sense organs Signal transduction Protein Processing Post-Translational Drosophila Protein Protein Binding Signal Transduction |
| Zdroj: | Nature cell biology |
| ISSN: | 1476-4679 1465-7392 |
| Popis: | 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 characterise 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 Ser413. Since Sik kinases have been implicated in nutrient sensing, this suggests a link between the Hippo pathway and systemic growth control. |
| Databáze: | OpenAIRE |
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