ArticlePLoS genetics2010
Dynamic switch of negative feedback regulation in Drosophila Akt-TOR signaling.
Article in PLoS genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 60 citations in OpenAlex.
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- PANGEA: a new gene set enrichment tool for Drosophila and common research organisms.Nucleic acids research · 2023Article
- PANGEA: A New Gene Set Enrichment Tool forbioRxiv : the preprint server for biology · 2023Article
- A genetic strategy to measure insulin signaling regulation and physiology in Drosophila.PLoS genetics · 2023Article
- Heritable shifts in redox metabolites during mitochondrial quiescence reprogramme progeny metabolism.Nature metabolism · 2021Article
- Discovering signaling mechanisms governing metabolism and metabolic diseases with Drosophila.Cell metabolism · 2021Review
- Article
- The Splicing Factor SF2 Is Critical for Hyperproliferation and Survival in a TORC1-Dependent Model of Early Tumorigenesis inInternational journal of molecular sciences · 2020Article
- The Hippo pathway integrates PI3K-Akt signals with mechanical and polarity cues to control tissue growth.PLoS biology · 2019Article
- TRiC/CCT chaperonins are essential for organ growth by interacting with insulin/TOR signaling in Drosophila.Oncogene · 2019Article
- Article
- iProteinDB: An Integrative Database ofG3 (Bethesda, Md.) · 2019Article
- FoxO restricts growth and differentiation of cells with elevated TORC1 activity under nutrient restriction.PLoS genetics · 2018Article
- ADisease models & mechanisms · 2017Article
- Regulation of Carbohydrate Energy Metabolism inGenetics · 2017Review
- An Integrative Analysis of the InR/PI3K/Akt Network Identifies the Dynamic Response to Insulin Signaling.Cell reports · 2016Article
- Drosophila Spidey/Kar Regulates Oenocyte Growth via PI3-Kinase Signaling.PLoS genetics · 2016Article
- Using Drosophila to discover mechanisms underlying type 2 diabetes.Disease models & mechanisms · 2016Review
- Cyclin G Functions as a Positive Regulator of Growth and Metabolism in Drosophila.PLoS genetics · 2015Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Akt represents a nodal point between the Insulin receptor and TOR signaling, and its activation by phosphorylation controls cell proliferation, cell size, and metabolism. The activity of Akt must be carefully balanced, as increased Akt signaling is frequently associated with cancer and as insufficient Akt signaling is linked to metabolic disease and diabetes mellitus. Using a genome-wide RNAi screen in Drosophila cells in culture, and in vivo analyses in the third instar wing imaginal disc, we studied the regulatory circuitries that define dAkt activation. We provide evidence that negative feedback regulation of dAkt occurs during normal Drosophila development in vivo. Whereas in cell culture dAkt is regulated by S6 Kinase (S6K)-dependent negative feedback, this feedback inhibition only plays a minor role in vivo. In contrast, dAkt activation under wild-type conditions is defined by feedback inhibition that depends on TOR Complex 1 (TORC1), but is S6K-independent. This feedback inhibition is switched from TORC1 to S6K only in the context of enhanced TORC1 activity, as triggered by mutations in tsc2. These results illustrate how the Akt-TOR pathway dynamically adapts the routing of negative feedback in response to the activity load of its signaling circuit in vivo.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.