title: Drosophila's insulin/PI3-kinase pathway coordinates cellular metabolism with nutritional conditions.
abstract: Studies in Drosophila have characterized insulin receptor/phosphoinositide 3-kinase (Inr/PI3K) signaling as a potent regulator of cell growth, but its function during development has remained uncertain. Here we show that inhibiting Inr/PI3K signaling phenocopies the cellular and organismal effects of starvation, whereas activating this pathway bypasses the nutritional requirement for cell growth, causing starvation sensitivity at the organismal level. Consistent with these findings, studies using a pleckstrin homology domain-green fluorescent protein (PH-GFP) fusion as an indicator for PI3K activity show that PI3K is regulated by the availability of dietary protein in vivo. Hence we surmise that an essential function of insulin/PI3K signaling in Drosophila is to coordinate cellular metabolism with nutritional conditions.
authors.affiliation: Molecular and Cellular Biology Program, Seattle, WA 98109, USA.
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Britton
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Lockwood
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Cohen
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Edgar
mesh_terms: D000595:Amino Acid Sequence; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D030801:Animals, Genetically Modified; D001798:Blood Proteins / Q000737:chemistry / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D004044:Dietary Proteins / Q000378:metabolism / Q000494:pharmacology*; D004330:Drosophila / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D005216:Fat Body / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism; D005247:Feeding Behavior; D005753:Gastric Mucosa / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007814:Larva / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D008969:Molecular Sequence Data; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics; D017434:Protein Structure, Tertiary; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013217:Starvation / Q000378:metabolism; D013270:Stomach / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D015996:Survival Rate; D019076:Transgenes / Q000235:genetics
chemical_list: D001798:Blood Proteins; D004044:Dietary Proteins; D007328:Insulin; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010750:Phosphoproteins; D011972:Receptor, Insulin; C039077:platelet protein P47