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

Authors: Wehr, M.; Holder, M.; Gailite, I.; Saunders, R.; Maile, T.; Ciirdaeva, E.; Instrell, R.; +4 Authors

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

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.

Keywords

Intracellular Signaling Peptides and Proteins, Nuclear Proteins, Cell Cycle Proteins, Organ Size, Protein Serine-Threonine Kinases, Article, Cell Line, Drosophila melanogaster, 14-3-3 Proteins, Gene Expression Regulation, Gene Knockdown Techniques, Protein Interaction Mapping, Trans-Activators, Animals, Drosophila Proteins, Wings, Animal, RNA Interference, Phosphorylation, Protein Processing, Post-Translational, Protein Binding, Signal Transduction

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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    99
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
99
Top 10%
Top 10%
Top 10%
Green
hybrid