Insulin/TOR signaling in growth and homeostasis: a view from the fly world.
The insulin/TOR pathway is a conserved regulator of cell and organism growth in metazoans. Over the last several years, an array of signaling inputs to this pathway has been defined. However the growth-regulatory outputs are less clear. Drosophila has proven to be a powerful genetic model system in which to study insulin/TOR signaling. This review highlights recent studies in Drosophila that have identified essential outputs and key effectors of the pathway. These include the regulation of ribosome synthesis, mRNA translation, autophagy and endocytosis, through downstream effectors such as Myc, FOXO, HIF1-alpha, TIF-IA, 4EBP and Atg1. This network of outputs and effectors can regulate cell and organismal metabolism, and is essential for the control of tissue growth, responses to starvation and stress, and aging. The mechanisms identified in Drosophila likely operate in most metazoans, and are relevent to our understanding of diseases caused by aberrent insulin/TOR signaling such as cancer, diabetes and obesity.
Grewal
Savraj S
SS
Southern Alberta Cancer Research Institute, Department of Biochemistry and Molecular Biology, University of Calgary, 3330 Hospital Drive, Calgary, AB T2N4N1, Canada. grewalss@ucalgary.ca
D000818:Animals; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011494:Protein Kinases; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
D029721:Drosophila Proteins; D007328:Insulin; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D058570:TOR Serine-Threonine Kinases; C416303:target of rapamycin protein, Drosophila