Genomes and Genes
Gene Symbol: Pi3K92E
Alias: CG4141, DP110, Dmel\CG4141, Dmp110, Dp110, Dp110/PI3K, Dpp110, PI(3)K, PI-3 kinase, PI-3-K, PI3'K, PI3K, PI3K-92D, PI3K-92E/Dp110, PI3K-Dp110, PI3K-I, PI3K-dp110, PI3K92E, PI3k, PI[]K, Pi3K, Pi3K92D, Pi3K92E, p110, Pi3Kp110, Pi3k, Pi3k92e, PiK92E, anon-92Ed, dP110, dP13K, dPI3K, dPI3K[92E], dp110, dp110alpha, p110, p120, pi3k, pi3k92e, rea, type-1 PI3K, Pi3K92E, CG4141-PA, CG4141-PB, CG4141-PC, PI 3-kinase, PI3 kinase, PI3-kinase, PI3Kinase92E, Phosphatidylinositol-3-kinase, Phosphoinositide-3 kinase, Pi3K92E-PA, Pi3K92E-PB, Pi3K92E-PC, class I PI(3)K, dPI 3-kinase, insulin-regulated PI3 kinase, p110 PI3 kinase, phosphatidylinositol 3-kinase, phosphatidylinositol-3 kinase, phospho-inositol-3 kinase at 92E, phosphoinositide 3 kinase Dp110, phosphoinositide 3-kinase, phosphotidylinositol 3 kinase
Species: fruit fly
- Acebes A, Martín Peña A, Chevalier V, Ferrús A. Synapse loss in olfactory local interneurons modifies perception. J Neurosci. 2011;31:2734-45 pubmed publisher..Here we modified a PI3K/AKT/GSK3 signaling pathway to reduce the number of synapses--without affecting the number of cells--in five subsets ..
- Zhang W, Thompson B, Hietakangas V, Cohen S. MAPK/ERK signaling regulates insulin sensitivity to control glucose metabolism in Drosophila. PLoS Genet. 2011;7:e1002429 pubmed publisher..The MAPK/ERK pathway acts via the ETS-1 transcription factor Pointed. This mechanism permits physiological adjustment of insulin sensitivity and subsequent maintenance of circulating glucose at appropriate levels. ..
- Weinkove D, Neufeld T, Twardzik T, Waterfield M, Leevers S. Regulation of imaginal disc cell size, cell number and organ size by Drosophila class I(A) phosphoinositide 3-kinase and its adaptor. Curr Biol. 1999;9:1019-29 pubmed..Overexpression of the gene encoding the Drosophila class I(A) PI 3-kinase, Dp110, in imaginal discs, however, results in enlarged adult organs...
- Willecke M, Toggweiler J, Basler K. Loss of PI3K blocks cell-cycle progression in a Drosophila tumor model. Oncogene. 2011;30:4067-74 pubmed publisher..We found that reduction of phosphoinositide 3-kinase (PI3K) activity resulted in very small tumors while only slightly affecting growth of wild-type tissue...
- Wu Q, Brown M. Signaling and function of insulin-like peptides in insects. Annu Rev Entomol. 2006;51:1-24 pubmed
- Jünger M, Rintelen F, Stocker H, Wasserman J, Végh M, Radimerski T, et al. The Drosophila forkhead transcription factor FOXO mediates the reduction in cell number associated with reduced insulin signaling. J Biol. 2003;2:20 pubmed..We propose that in response to cellular stresses, such as nutrient deprivation or increased levels of reactive oxygen species, dFOXO is activated and inhibits growth through the action of target genes such as d4E-BP. ..
- Bohni R, Riesgo Escovar J, Oldham S, Brogiolo W, Stocker H, Andruss B, et al. Autonomous control of cell and organ size by CHICO, a Drosophila homolog of vertebrate IRS1-4. Cell. 1999;97:865-75 pubmed
- Fulga T, Rørth P. Invasive cell migration is initiated by guided growth of long cellular extensions. Nat Cell Biol. 2002;4:715-9 pubmed..We discuss similarities between LCEs and axons and the use of LCE-like structures as a general mechanism for initiating invasive migration in vivo. ..
- Pan D, Dong J, Zhang Y, Gao X. Tuberous sclerosis complex: from Drosophila to human disease. Trends Cell Biol. 2004;14:78-85 pubmed..Here, we review these exciting developments with an emphasis on Drosophila studies and discuss how Drosophila can be a powerful model system for an understanding of the molecular mechanisms of the activity of human disease genes. ..
- Cheng L, Bailey A, Leevers S, Ragan T, Driscoll P, Gould A. Anaplastic lymphoma kinase spares organ growth during nutrient restriction in Drosophila. Cell. 2011;146:435-47 pubmed publisher..Together, these findings identify a brain-sparing mechanism that shares some regulatory features with the starvation-resistant growth programs of mammalian tumors. ..
- Teleman A, Chen Y, Cohen S. Drosophila Melted modulates FOXO and TOR activity. Dev Cell. 2005;9:271-81 pubmedThe insulin/PI3K signaling pathway controls both tissue growth and metabolism. Here, we identify Melted as a new modulator of this pathway in Drosophila...
- Hyun S, Lee J, Jin H, Nam J, Namkoong B, Lee G, et al. Conserved MicroRNA miR-8/miR-200 and its target USH/FOG2 control growth by regulating PI3K. Cell. 2009;139:1096-108 pubmed publisher..Fat body-specific expression and clonal analyses reveal that miR-8 activates PI3K, thereby promoting fat cell growth cell-autonomously and enhancing organismal growth non-cell-autonomously...
- Acebes A, Devaud J, Arnés M, Ferrús A. Central adaptation to odorants depends on PI3K levels in local interneurons of the antennal lobe. J Neurosci. 2012;32:417-22 pubmed publisherWe have previously shown that driving PI3K levels up or down leads to increases or reductions in the number of synapses, respectively...
- Oldham S, Bohni R, Stocker H, Brogiolo W, Hafen E. Genetic control of size in Drosophila. Philos Trans R Soc Lond B Biol Sci. 2000;355:945-52 pubmed..In this article we will review recent evidence from vertebrates and particularly from Drosophila that implicates insulin/insulin-like growth factor-I and other growth pathways in the control of cell, organ and body size. ..
- Goberdhan D, Meredith D, Boyd C, Wilson C. PAT-related amino acid transporters regulate growth via a novel mechanism that does not require bulk transport of amino acids. Development. 2005;132:2365-75 pubmed..As PATH is likely to be saturated in vivo, we propose that one specialised function of high-affinity PAT-related molecules is to maintain growth as local nutrient levels fluctuate during development. ..
- Hall D, Grewal S, de la Cruz A, Edgar B. Rheb-TOR signaling promotes protein synthesis, but not glucose or amino acid import, in Drosophila. BMC Biol. 2007;5:10 pubmed..signaling components, suggesting that cellular energy levels and TOR activity can be maintained through insulin/PI3K-independent mechanisms in S2 cell culture...
- Kockel L, Kerr K, Melnick M, Brückner K, Hebrok M, Perrimon N. Dynamic switch of negative feedback regulation in Drosophila Akt-TOR signaling. PLoS Genet. 2010;6:e1000990 pubmed publisher..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. ..
- Prober D, Edgar B. Interactions between Ras1, dMyc, and dPI3K signaling in the developing Drosophila wing. Genes Dev. 2002;16:2286-99 pubmed..that Ras(V12) promotes cell growth and G(1)/S progression by increasing dMyc protein levels and activating dPI3K signaling, and that it does so via separate effector pathways...
- Miron M, Lasko P, Sonenberg N. Signaling from Akt to FRAP/TOR targets both 4E-BP and S6K in Drosophila melanogaster. Mol Cell Biol. 2003;23:9117-26 pubmed..Although S6K phosphorylation is independent of phosphoinositide 3-OH kinase (PI3K) and serine/threonine protein kinase Akt, that of 4E-BP is dependent on PI3K and Akt...
- Li L, Edgar B, Grewal S. Nutritional control of gene expression in Drosophila larvae via TOR, Myc and a novel cis-regulatory element. BMC Cell Biol. 2010;11:7 pubmed publisher..The conserved insulin/PI3K and TOR signaling pathways mediate nutrition-dependent growth in Drosophila and other animals...
- Oldham S, Hafen E. Insulin/IGF and target of rapamycin signaling: a TOR de force in growth control. Trends Cell Biol. 2003;13:79-85 pubmed..This review summarizes current studies primarily from Drosophila regarding the function of the insulin/IGF system in the control of growth. ..
- Teleman A, Maitra S, Cohen S. Drosophila lacking microRNA miR-278 are defective in energy homeostasis. Genes Dev. 2006;20:417-22 pubmed..We provide evidence that miR-278 mutants are insulin resistant and that miR-278 acts through regulation of the expanded transcript. ..
- Walker J, Tchoudakova A, McKenney P, Brill S, Wu D, Cowley G, et al. Reduced growth of Drosophila neurofibromatosis 1 mutants reflects a non-cell-autonomous requirement for GTPase-Activating Protein activity in larval neurons. Genes Dev. 2006;20:3311-23 pubmed
- Honegger B, Galic M, Kohler K, Wittwer F, Brogiolo W, Hafen E, et al. Imp-L2, a putative homolog of vertebrate IGF-binding protein 7, counteracts insulin signaling in Drosophila and is essential for starvation resistance. J Biol. 2008;7:10 pubmed publisher..Given that Imp-L2 and the human tumor suppressor IGFBP-7 show sequence homology in their carboxy-terminal immunoglobulin-like domains, we suggest that their common precursor was an ancestral insulin-binding protein. ..
- Colombani J, Raisin S, Pantalacci S, Radimerski T, Montagne J, Leopold P. A nutrient sensor mechanism controls Drosophila growth. Cell. 2003;114:739-49 pubmed..Our results demonstrate that the fat body functions as a nutrient sensor that restricts global growth through a humoral mechanism. ..
- Clemens J, Worby C, Simonson Leff N, Muda M, Maehama T, Hemmings B, et al. Use of double-stranded RNA interference in Drosophila cell lines to dissect signal transduction pathways. Proc Natl Acad Sci U S A. 2000;97:6499-503 pubmed
- Gao X, Neufeld T, Pan D. Drosophila PTEN regulates cell growth and proliferation through PI3K-dependent and -independent pathways. Dev Biol. 2000;221:404-18 pubmed..The loss-of-function phenotypes of dPTEN are suppressed by mutations in the PI3K target Dakt1 and the translational initiation factor eif4A, suggesting that dPTEN acts through the PI3K signaling ..
- Williams K, Busto M, Suster M, So A, Ben Shahar Y, Leevers S, et al. Natural variation in Drosophila melanogaster diapause due to the insulin-regulated PI3-kinase. Proc Natl Acad Sci U S A. 2006;103:15911-5 pubmed..overwintering strategy, diapause, to the insulin-regulated phosphatidylinositol 3-kinase (PI3-kinase) gene, Dp110. Variation in diapause, a reproductive arrest, was associated with Dp110 by using Dp110 deletions and genomic ..
- Caldwell P, Walkiewicz M, Stern M. Ras activity in the Drosophila prothoracic gland regulates body size and developmental rate via ecdysone release. Curr Biol. 2005;15:1785-95 pubmed..Here, we show that the expression of activated Ras, PI3 kinase (PI3K), or Raf specifically in the PG reduces body size, whereas activated Ras or PI3K, but not Raf, increases ..
- King Jones K, Thummel C. Developmental biology. Less steroids make bigger flies. Science. 2005;310:630-1 pubmed
- Rintelen F, Stocker H, Thomas G, Hafen E. PDK1 regulates growth through Akt and S6K in Drosophila. Proc Natl Acad Sci U S A. 2001;98:15020-5 pubmed..and vertebrates by increasing the levels of phosphatidylinositol 3,4,5-triphosphate through the activation of p110 phosphatidylinositol 3-kinase...
- Howlett E, Lin C, Lavery W, Stern M. A PI3-kinase-mediated negative feedback regulates neuronal excitability. PLoS Genet. 2008;4:e1000277 pubmed publisher..We show that DmGluRA mutations increase neuronal excitability by preventing PI3 kinase (PI3K) activation and consequently hyperactivating the transcription factor Foxo...
- MacDougall L, Gagou M, Leevers S, Hafen E, Waterfield M. Targeted expression of the class II phosphoinositide 3-kinase in Drosophila melanogaster reveals lipid kinase-dependent effects on patterning and interactions with receptor signaling pathways. Mol Cell Biol. 2004;24:796-808 pubmed..We have obtained the first evidence for a biological function for a class II PI3K by expressing this enzyme during Drosophila melanogaster development and by using deficiencies that remove the ..
- Colombani J, Bianchini L, Layalle S, Pondeville E, Dauphin Villemant C, Antoniewski C, et al. Antagonistic actions of ecdysone and insulins determine final size in Drosophila. Science. 2005;310:667-70 pubmed..Hence, ecdysone counteracts the growth-promoting action of insulins, thus forming a humoral regulatory loop that determines organismal size. ..
- O Farrell F, Wang S, Katheder N, Rusten T, Samakovlis C. Two-tiered control of epithelial growth and autophagy by the insulin receptor and the ret-like receptor, stitcher. PLoS Biol. 2013;11:e1001612 pubmed publisher..Ret-like receptor tyrosine kinase (RTK), Stitcher (Stit), is required for cell growth and proliferation through the PI3K-I/TORC1 pathway in the Drosophila wing disc...
- Radimerski T, Montagne J, Rintelen F, Stocker H, van der Kaay J, Downes C, et al. dS6K-regulated cell growth is dPKB/dPI(3)K-independent, but requires dPDK1. Nat Cell Biol. 2002;4:251-5 pubmed
- Day S, Lawrence P. Measuring dimensions: the regulation of size and shape. Development. 2000;127:2977-87 pubmed..We discuss a hypothesis that the local steepness of a morphogen gradient is a measure of length in one axis, a measure that is used to determine whether there will be net growth or not. ..
- Sousa Nunes R, Yee L, Gould A. Fat cells reactivate quiescent neuroblasts via TOR and glial insulin relays in Drosophila. Nature. 2011;471:508-12 pubmed publisher..Downstream of this signal, Insulin-like receptor signalling and the Phosphatidylinositol 3-kinase (PI3K)/TOR network are required in neuroblasts for exit from quiescence...
- Halfar K, Rommel C, Stocker H, Hafen E. Ras controls growth, survival and differentiation in the Drosophila eye by different thresholds of MAP kinase activity. Development. 2001;128:1687-96 pubmed..Low MAPK activity prolongs cell survival and permits differentiation of R8 photoreceptor cells while high or persistent MAPK activity is sufficient to precociously induce R1-R7 photoreceptor differentiation in dividing cells. ..
- Hennig K, Neufeld T. Inhibition of cellular growth and proliferation by dTOR overexpression in Drosophila. Genesis. 2002;34:107-10 pubmed
- Zhao X, Campos A. Insulin signalling in mushroom body neurons regulates feeding behaviour in Drosophila larvae. J Exp Biol. 2012;215:2696-702 pubmed publisher..Here, we show that impairment of insulin signalling in the mushroom body neurons, a structure involved in associative learning, impairs feeding behaviour in the Drosophila larva. ..
- Goberdhan D, Paricio N, Goodman E, Mlodzik M, Wilson C. Drosophila tumor suppressor PTEN controls cell size and number by antagonizing the Chico/PI3-kinase signaling pathway. Genes Dev. 1999;13:3244-58 pubmed..DPTEN modulates tissue mass by acting antagonistically to the Drosophila Class I phosphatidylinositol 3-kinase, Dp110, and its upstream activator Chico, an insulin receptor substrate homolog...
- Brückner K, Kockel L, Duchek P, Luque C, Rørth P, Perrimon N. The PDGF/VEGF receptor controls blood cell survival in Drosophila. Dev Cell. 2004;7:73-84 pubmed..This function of PVR shows striking conservation with mammalian hematopoiesis and establishes Drosophila as a model to study hematopoietic cell survival in development and disease. ..
- Bateman J, McNeill H. Temporal control of differentiation by the insulin receptor/tor pathway in Drosophila. Cell. 2004;119:87-96 pubmed..tsc1 controls the timing of differentiation downstream or in parallel to the RAS/MAPK pathway. Examination of InR, PI3K, PTEN, Tor, Rheb, and S6 kinase mutants demonstrates that increased InR signaling leads to precocious ..
- Ninov N, Manjón C, Martin Blanco E. Dynamic control of cell cycle and growth coupling by ecdysone, EGFR, and PI3K signaling in Drosophila histoblasts. PLoS Biol. 2009;7:e1000079 pubmed publisher..growth factor receptor (EGFR) signaling for progression through the G2/M transition and on insulin receptor/PI3K-mediated signaling for growth...
- Orme M, Alrubaie S, Bradley G, Walker C, Leevers S. Input from Ras is required for maximal PI(3)K signalling in Drosophila. Nat Cell Biol. 2006;8:1298-302 pubmed..The Drosophila class I PI(3)K, Dp110, is activated by nutrient-responsive insulin signalling and modulates growth, oogenesis and metabolism...
- de la Cova C, Abril M, Bellosta P, Gallant P, Johnston L. Drosophila myc regulates organ size by inducing cell competition. Cell. 2004;117:107-16 pubmed..Modulating dmyc levels to create cell competition and hid-dependent cell death may be a mechanism used during normal development to control organ size. ..
- Leevers S, Weinkove D, MacDougall L, Hafen E, Waterfield M. The Drosophila phosphoinositide 3-kinase Dp110 promotes cell growth. EMBO J. 1996;15:6584-94 pubmed..Here we describe the molecular and functional analysis of Drosophila p110 (Dp110)...
- Mirth C, Truman J, Riddiford L. The role of the prothoracic gland in determining critical weight for metamorphosis in Drosophila melanogaster. Curr Biol. 2005;15:1796-807 pubmed..We present evidence that in Drosophila, a component of the ring gland, the prothoracic gland (PG), assesses growth to determine when critical weight has been achieved...
- Froldi F, Ziosi M, Garoia F, Pession A, Grzeschik N, Bellosta P, et al. The lethal giant larvae tumour suppressor mutation requires dMyc oncoprotein to promote clonal malignancy. BMC Biol. 2010;8:33 pubmed publisher..Moreover, we show that dMyc abundance inside versus outside the mutant clones plays a key role in driving neoplastic overgrowth. ..
- Manning B, Cantley L. Rheb fills a GAP between TSC and TOR. Trends Biochem Sci. 2003;28:573-6 pubmed
- Britton J, Lockwood W, Li L, Cohen S, Edgar B. Drosophila's insulin/PI3-kinase pathway coordinates cellular metabolism with nutritional conditions. Dev Cell. 2002;2:239-49 pubmedStudies 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...
- Slaidina M, Delanoue R, Gronke S, Partridge L, Leopold P. A Drosophila insulin-like peptide promotes growth during nonfeeding states. Dev Cell. 2009;17:874-84 pubmed publisher..This study reveals a specific class of ILPs induced upon metabolic stress that promotes growth in conditions of nutritional deprivation or following developmentally induced cessation of feeding. ..
- Scanga S, Ruel L, Binari R, Snow B, Stambolic V, Bouchard D, et al. The conserved PI3'K/PTEN/Akt signaling pathway regulates both cell size and survival in Drosophila. Oncogene. 2000;19:3971-7 pubmed..This study therefore establishes the evolutionary conservation of this signaling pathway in Drosophila. Oncogene (2000) 19, 3971 - 3977. ..
- Wu Q, Zhang Y, Xu J, Shen P. Regulation of hunger-driven behaviors by neural ribosomal S6 kinase in Drosophila. Proc Natl Acad Sci U S A. 2005;102:13289-94 pubmed..Our study reveals a prominent role of neural Drosophila p70/S6 kinase in the modulation of hunger response by insulin-like and neuropeptide Y-like signaling pathways. ..
- Mirth C, Truman J, Riddiford L. The ecdysone receptor controls the post-critical weight switch to nutrition-independent differentiation in Drosophila wing imaginal discs. Development. 2009;136:2345-53 pubmed publisher..These results suggest that post-critical weight, EcR signaling switches wing discs to a nutrition-independent mode of development via derepression. ..
- Reiling J, Hafen E. The hypoxia-induced paralogs Scylla and Charybdis inhibit growth by down-regulating S6K activity upstream of TSC in Drosophila. Genes Dev. 2004;18:2879-92 pubmed
- Moreno E, Basler K. dMyc transforms cells into super-competitors. Cell. 2004;117:117-29 pubmed..Hence the heritable increase in dMyc levels causes cells to behave as "super-competitors" and reveals a novel mode of clonal expansion that causes, but also relies on, the killing of surrounding cells. ..
- Jones M, Gargano J, Rhodenizer D, Martin I, Bhandari P, Grotewiel M. A forward genetic screen in Drosophila implicates insulin signaling in age-related locomotor impairment. Exp Gerontol. 2009;44:532-40 pubmed publisher..loss of function mutations in PDK1 as well as loss of function alleles of two other insulin signaling genes, Dp110 and Akt (the genes for the catalytic subunit of phosphoinositide 3-kinase and AKT), also forestalled ARLI...
- Teleman A. Molecular mechanisms of metabolic regulation by insulin in Drosophila. Biochem J. 2009;425:13-26 pubmed publisher..I discuss both the intracellular signalling network, as well as the communication between organs in the fly. ..
- McNeill H, Craig G, Bateman J. Regulation of neurogenesis and epidermal growth factor receptor signaling by the insulin receptor/target of rapamycin pathway in Drosophila. Genetics. 2008;179:843-53 pubmed publisher..Together these data suggest that InR/TOR signaling regulates the timing of differentiation through modulation of EGFR target genes in developing photoreceptors. ..
- Parisi F, Riccardo S, Daniel M, Saqcena M, Kundu N, Pession A, et al. Drosophila insulin and target of rapamycin (TOR) pathways regulate GSK3 beta activity to control Myc stability and determine Myc expression in vivo. BMC Biol. 2011;9:65 pubmed publisher..by insulin and TOR pathways is a mechanism conserved in cells from the wing imaginal disc, where expression of Dp110 and Rheb also induces Myc protein accumulation, while inhibition of insulin and TOR pathways result in the ..
- Scott R, Schuldiner O, Neufeld T. Role and regulation of starvation-induced autophagy in the Drosophila fat body. Dev Cell. 2004;7:167-78 pubmed..Here, we show that signaling through TOR and its upstream regulators PI3K and Rheb is necessary and sufficient to suppress starvation-induced autophagy in the Drosophila fat body...
- Huang H, Potter C, Tao W, Li D, Brogiolo W, Hafen E, et al. PTEN affects cell size, cell proliferation and apoptosis during Drosophila eye development. Development. 1999;126:5365-72 pubmed
- Rusten T, Lindmo K, Juhasz G, Sass M, Seglen P, Brech A, et al. Programmed autophagy in the Drosophila fat body is induced by ecdysone through regulation of the PI3K pathway. Dev Cell. 2004;7:179-92 pubmed..The Tor and PI3K signaling pathways have been shown to negatively control autophagy in eukaryotes, but the mechanisms that link ..
- Grewal S, Li L, Orian A, Eisenman R, Edgar B. Myc-dependent regulation of ribosomal RNA synthesis during Drosophila development. Nat Cell Biol. 2005;7:295-302 pubmed..In addition, the growth effects of dMyc in larval wing imaginal discs require de novo rRNA synthesis. We suggest that during animal development, the control of rRNA synthesis and ribosome biogenesis is an essential Myc function. ..
- Werz C, Kohler K, Hafen E, Stocker H. The Drosophila SH2B family adaptor Lnk acts in parallel to chico in the insulin signaling pathway. PLoS Genet. 2009;5:e1000596 pubmed publisher..epistasis analysis places lnk downstream of the insulin receptor (InR) and upstream of phosphoinositide 3-kinase (PI3K) in the IIS cascade, at the same level as chico (encoding the single fly insulin receptor substrate [IRS] homolog)...