Gene Symbol: Pi3K21B
Description: Pi3K21B
Alias: CG2699, Dmel\CG2699, Dp60, PI(3)K, PI3K, PI3K-p60, PI3K21B, PI[[3]]K, Pi3K21B, p60, Pi3Kp60, Pi3k21B, dP60, dPI3K, droPIK57, p60, Pi3K21B, CG2699-PB, CG2699-PC, CG2699-PD, CG2699-PE, PI 3-kinase, PI3 kinase, PI3-kinase, Pi3K21B-PB, Pi3K21B-PC, Pi3K21B-PD, Pi3K21B-PE, dPI 3-kinase
Species: fruit fly

Top Publications

  1. 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
    ..These observations have led us to investigate the role of Dp100 and its adaptor, p60, in the control of imaginal disc cell size, cell number and organ size...
  2. Weinkove D, Leevers S, MacDougall L, Waterfield M. p60 is an adaptor for the Drosophila phosphoinositide 3-kinase, Dp110. J Biol Chem. 1997;272:14606-10 pubmed
    ..Here we show that a heterodimer of the Drosophila PI3K, Dp110, with an adaptor, p60, can be purified from S2 cells with a pYXXM phosphopeptide affinity matrix...
  3. 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. ..
  4. 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
    ..These data imply a role for Dp110 in growth control during Drosophila development and have implications for the function of class I PI3Ks in other organisms. ..
  5. Oldham S, Stocker H, Laffargue M, Wittwer F, Wymann M, Hafen E. The Drosophila insulin/IGF receptor controls growth and size by modulating PtdInsP(3) levels. Development. 2002;129:4103-9 pubmed
    ..Drk/Grb2 in Chico/IRS does not interfere with growth whereas mutating the binding sites of the PI 3-kinase adaptor p60 completely abrogates Chico function...
  6. Oldham S, Montagne J, Radimerski T, Thomas G, Hafen E. Genetic and biochemical characterization of dTOR, the Drosophila homolog of the target of rapamycin. Genes Dev. 2000;14:2689-94 pubmed
    ..These results are consistent with dTOR residing on a parallel amino acid sensing pathway. ..
  7. Hsu H, LaFever L, Drummond Barbosa D. Diet controls normal and tumorous germline stem cells via insulin-dependent and -independent mechanisms in Drosophila. Dev Biol. 2008;313:700-12 pubmed
    ..Here, we report that DILPs specifically control the G2 phase of the GSC cell cycle via phosphoinositide-3 kinase (PI3K) and dFOXO, and that a separate diet mediator regulates the G1 phase...
  8. 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...
  9. Wittwer F, Jaquenoud M, Brogiolo W, Zarske M, Wüstemann P, Fernandez R, et al. Susi, a negative regulator of Drosophila PI3-kinase. Dev Cell. 2005;8:817-27 pubmed
    ..We provide genetic evidence that Susi negatively regulates dPI3K activity. Susi directly binds to dP60, the regulatory subunit of dPI3K...

More Information


  1. Delanoue R, Slaidina M, Leopold P. The steroid hormone ecdysone controls systemic growth by repressing dMyc function in Drosophila fat cells. Dev Cell. 2010;18:1012-21 pubmed publisher
    ..In conclusion, the present work reveals an unexpected function of dMyc in the systemic control of growth in response to steroid hormone signaling. ..
  2. 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. ..
  3. Wymann M, Pirola L. Structure and function of phosphoinositide 3-kinases. Biochim Biophys Acta. 1998;1436:127-50 pubmed
    ..Recent disruption of PI3K genes in slime mold, Caenorhabditis elegans, Drosophila melanogaster and mice further underlines the importance of ..
  4. 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
  5. Das T, Dana D, Paroly S, Perumal S, Singh S, Jhun H, et al. Centrosomal kinase Nek2 cooperates with oncogenic pathways to promote metastasis. Oncogenesis. 2013;2:e69 pubmed publisher
    ..Inhibition of the PI3K pathway suppressed the cooperation of dNek2 with other growth pathways...
  6. Yang L, Baker N. Cell cycle withdrawal, progression, and cell survival regulation by EGFR and its effectors in the differentiating Drosophila eye. Dev Cell. 2003;4:359-69 pubmed
    ..Our results suggest that, rather than triggering all or none responses, EGFR coordinates partially independent processes as the eye differentiates. ..
  7. Corty M, Freeman M. Cell biology in neuroscience: Architects in neural circuit design: glia control neuron numbers and connectivity. J Cell Biol. 2013;203:395-405 pubmed publisher
    ..Recent findings illustrate the importance of glial cells in shaping the nervous system by controlling the number and connectivity of neurons. ..
  8. Leevers S. Growth control: invertebrate insulin surprises!. Curr Biol. 2001;11:R209-12 pubmed
    ..Invertebrates have been found to possess more insulin-like ligands than predicted, some of which behave as receptor antagonists. ..
  9. Ishimaru S, Ueda R, Hinohara Y, Ohtani M, Hanafusa H. PVR plays a critical role via JNK activation in thorax closure during Drosophila metamorphosis. EMBO J. 2004;23:3984-94 pubmed
    ..In addition, we suppose that not only Rac but also Cdc42 is activated and involved in JNK activation downstream of PVR. ..
  10. Glatter T, Schittenhelm R, Rinner O, Roguska K, Wepf A, Jünger M, et al. Modularity and hormone sensitivity of the Drosophila melanogaster insulin receptor/target of rapamycin interaction proteome. Mol Syst Biol. 2011;7:547 pubmed publisher
    ..Subsequent genetic studies in flies suggest a role for dTTT in controlling cell growth via a dTORC1- and dTORC2-dependent mechanism. ..
  11. Stambolic V, Mak T, Woodgett J. Modulation of cellular apoptotic potential: contributions to oncogenesis. Oncogene. 1999;18:6094-103 pubmed
    ..This review focuses on the regulation and mechanisms by which PKB activation protects cells and the oncologic consequences of dysregulation of the pathway. ..
  12. Partridge L, Gems D, Withers D. Sex and death: what is the connection?. Cell. 2005;120:461-72 pubmed
    ..Understanding the molecular basis of the cost of reproduction will be informed by elucidation of the mechanisms by which DR and IIS affect these two traits. ..
  13. Leopold P. Neuronal differentiation: TOR and insulin receptor pathways set the tempo. Cell. 2004;119:4-5 pubmed
    ..A recent study reveals a novel role for these pathways in controlling the timing of neuronal differentiation during Drosophila development, thus allowing a tight coordination between growth and differentiation programs. ..
  14. Grewal S, Saucedo L. Chewing the fat; regulating autophagy in Drosophila. Dev Cell. 2004;7:148-50 pubmed
    ..Two reports in this issue of Developmental Cell describe how both PI3 kinase and TOR signaling in Drosophila are critical for controlling autophagy in response to developmental and ..
  15. Siegrist S, Haque N, Chen C, Hay B, Hariharan I. Inactivation of both Foxo and reaper promotes long-term adult neurogenesis in Drosophila. Curr Biol. 2010;20:643-8 pubmed publisher
    ..Prior to their elimination, their growth and proliferation slows because of decreased insulin/PI3 kinase signaling, resulting in nuclear localization of Foxo...
  16. Strauss E. Longevity. Growing old together. Science. 2001;292:41-3 pubmed
  17. Vanhaesebroeck B, Leevers S, Panayotou G, Waterfield M. Phosphoinositide 3-kinases: a conserved family of signal transducers. Trends Biochem Sci. 1997;22:267-72 pubmed
    ..Potential signalling pathways downstream of PI3Ks have been elucidated and PI3K function is now being characterised in several model organisms.
  18. Miron M, Verdu J, Lachance P, Birnbaum M, Lasko P, Sonenberg N. The translational inhibitor 4E-BP is an effector of PI(3)K/Akt signalling and cell growth in Drosophila. Nat Cell Biol. 2001;3:596-601 pubmed
    ..Our results support a role for d4E-BP as an effector of cell growth. ..
  19. Chuang C, Lu Y, Wang H, Chang H. Genetic dissection reveals that Akt is the critical kinase downstream of LRRK2 to phosphorylate and inhibit FOXO1, and promotes neuron survival. Hum Mol Genet. 2014;23:5649-58 pubmed publisher
    ..These results might indicate that a LRRK-Akt therapeutic pathway to promote neuron survival and to prevent neurodegeneration in Parkinson's disease. ..
  20. 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 ..
  21. Alvarez Ponce D, Aguade M, Rozas J. Network-level molecular evolutionary analysis of the insulin/TOR signal transduction pathway across 12 Drosophila genomes. Genome Res. 2009;19:234-42 pubmed publisher
    ..Our results clearly indicate that the levels of functional constraint do depend on the position of the proteins in the pathway and, consequently, the architecture of the pathway constrains gene sequence evolution. ..
  22. Kim S, Cho J, Kim K, Lee S, Lee K, Choi K. Drosophila PI3 kinase and Akt involved in insulin-stimulated proliferation and ERK pathway activation in Schneider cells. Cell Signal. 2004;16:1309-17 pubmed
    ..After insulin treatment, dPI3K and dAKT activities were both increased along with activation of the dERK pathway components dMEK and dERK...
  23. Fernandes C, Rao Y. Genome-wide screen for modifiers of Parkinson's disease genes in Drosophila. Mol Brain. 2011;4:17 pubmed publisher
    ..Among them, opa1 and drp1 have been previously implicated in the PD pathways, whereas debra (dbr), Pi3K21B and ?4GalNAcTA are novel PD-interacting genes...
  24. Pierce S, Yost C, Britton J, Loo L, Flynn E, Edgar B, et al. dMyc is required for larval growth and endoreplication in Drosophila. Development. 2004;131:2317-27 pubmed
    ..By contrast, the ability of dMyc to promote growth and endoreplication is only partly reduced when PI3K activity is blocked, suggesting that they influence distinct growth pathways...
  25. Wilson R, Leptin M. Fibroblast growth factor receptor-dependent morphogenesis of the Drosophila mesoderm. Philos Trans R Soc Lond B Biol Sci. 2000;355:891-5 pubmed
    ..Analysis of the function of dof, which encodes a cytoplasmic protein required for FGF signal transduction may provide an insight into these issues. ..
  26. Gumienny T, Padgett R. A small issue addressed. Bioessays. 2003;25:305-8 pubmed
    ..elegans, the TGFbeta-like pathway acts in the hypodermis to regulate cell size and consequently body size.1 This finding is an exciting step in discovering the molecular mechanisms that control cell and body size. ..
  27. Lehner C. The beauty of small flies. Nat Cell Biol. 1999;1:E129-30 pubmed
  28. Schweisguth F. Cell polarity: fixing cell polarity with Pins. Curr Biol. 2000;10:R265-7 pubmed
    ..A protein complex is assembled in a step-wise manner at the apical pole of Drosophila neuroblasts. This complex organizes the apical-basal polarity of asymmetrically dividing neuroblasts, and may act via G-protein signalling. ..
  29. Jorgensen P, Tyers M. How cells coordinate growth and division. Curr Biol. 2004;14:R1014-27 pubmed
    ..Recently, genetic screens in Drosophila and functional genomics approaches in yeast have macheted into the thicket of cell size control. ..
  30. Acevedo S, Peru y Colón de Portugal R, Gonzalez D, Rodan A, Rothenfluh A. S6 Kinase Reflects and Regulates Ethanol-Induced Sedation. J Neurosci. 2015;35:15396-402 pubmed publisher
    ..In addition, activity of S6k is regulated by acute ethanol exposure and by neuronal activity. S6k activity is therefore both an acute target of ethanol exposure and a regulator of ethanol's effects on behavior. ..
  31. Hardie R. Phototransduction: shedding light on translocation. Curr Biol. 2003;13:R775-7 pubmed
    ..New work has identified a phosphoinositide lipid binding domain in Drosophila arrestin and implicates PIP(3) in control of arrestin translocation. ..
  32. Marygold S, Leevers S. Growth signaling: TSC takes its place. Curr Biol. 2002;12:R785-7 pubmed
    ..Several new studies suggest that TSC1-TSC2 does this by inhibiting TOR and S6 kinase, and that PI 3-kinase-Akt signaling relieves this inhibition. ..
  33. Shelly S, Lukinova N, Bambina S, Berman A, Cherry S. Autophagy is an essential component of Drosophila immunity against vesicular stomatitis virus. Immunity. 2009;30:588-98 pubmed publisher
    ..Lastly, we showed that the antiviral response was controlled by the phosphatidylinositol 3-kinase (PI3K)-Akt-signaling pathway, which normally regulates autophagy in response to nutrient availability...
  34. 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
    ..Thus, Dp110 integrates inputs from its phosphotyrosine-binding adaptor and Ras to achieve maximal PI(3)K signalling in specific biological situations. ..
  35. Gingras A, Raught B, Sonenberg N. Regulation of translation initiation by FRAP/mTOR. Genes Dev. 2001;15:807-26 pubmed
  36. Qin Q, Pei J, Ancona V, Shaw B, Ficht T, de Figueiredo P. RNAi screen of endoplasmic reticulum-associated host factors reveals a role for IRE1alpha in supporting Brucella replication. PLoS Pathog. 2008;4:e1000110 pubmed publisher
    ..After validating this system by demonstrating a shared requirement for phosphoinositide 3-kinase (PI3K) activities in supporting Brucella infection in both host cell systems, we performed an RNAi screen of 240 genes, ..
  37. Ejeskär K, Vickes O, Kuchipudi A, Wettergren Y, Uv A, Rotter Sopasakis V. The Unique Non-Catalytic C-Terminus of P37delta-PI3K Adds Proliferative Properties In Vitro and In Vivo. PLoS ONE. 2015;10:e0127497 pubmed publisher
    The PI3K/Akt pathway is central for numerous cellular functions and is frequently deregulated in human cancers...
  38. Miller P, Obrik Uloho O, Phan M, Medrano C, Renier J, Thayer J, et al. The song of the old mother: reproductive senescence in female drosophila. Fly (Austin). 2014;8:127-39 pubmed publisher
    ..Understanding the genetic basis of reproductive senescence clarifies the nature of life-history trade-offs as well as potential ways to augment and/or limit female fertility in a variety of organisms. ..
  39. Stocker H, Hafen E. Genetic control of cell size. Curr Opin Genet Dev. 2000;10:529-35 pubmed
    ..Evidence is emerging for a signalling cascade conserved in evolution that links external nutrient sources to cell size. ..
  40. Ribeiro C, Dickson B. Sex peptide receptor and neuronal TOR/S6K signaling modulate nutrient balancing in Drosophila. Curr Biol. 2010;20:1000-5 pubmed publisher
    ..We propose that the brain uses these internal states to assign value to external sensory information from potential food sources, thereby guiding food choice and ensuring nutrient homeostasis. ..
  41. Jekely G, Sung H, Luque C, Rørth P. Regulators of endocytosis maintain localized receptor tyrosine kinase signaling in guided migration. Dev Cell. 2005;9:197-207 pubmed
    ..Cbl and Sprint both regulate early steps of RTK endocytosis. Thus, a physiological role of RTK endocytosis is to ensure localized intracellular response to guidance cues by stimulating spatial restriction of signaling. ..
  42. Jacinto E, Hall M. Tor signalling in bugs, brain and brawn. Nat Rev Mol Cell Biol. 2003;4:117-26 pubmed
    ..Furthermore, TOR, by associating with regulatory proteins and inhibiting phosphatases, controls the activity of multiphosphorylated effectors. ..
  43. Gallio M, Englund C, Kylsten P, Samakovlis C. Rhomboid 3 orchestrates Slit-independent repulsion of tracheal branches at the CNS midline. Development. 2004;131:3605-14 pubmed
    ..We propose that Egfr activation provides a necessary switch for the interpretation of a yet unknown repellent function of the midline. ..
  44. 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. ..
  45. Weinkove D, Leevers S. The genetic control of organ growth: insights from Drosophila. Curr Opin Genet Dev. 2000;10:75-80 pubmed
    ..Furthermore, the role of Drosophila homologues to human tumour suppressor genes and oncogenes in imaginal disc growth has been investigated. ..
  46. Tapon N, Moberg K, Hariharan I. The coupling of cell growth to the cell cycle. Curr Opin Cell Biol. 2001;13:731-7 pubmed
    ..This work has revealed interesting and unexpected relationships between mechanisms that regulate growth and the cell cycle machinery. ..
  47. Downward J, Leevers S. Trachealess--a new transcription factor target for PKB/Akt. Dev Cell. 2001;1:726-8 pubmed
    ..Applying a combined genetic and biochemical approach has led to the identification of a new protein kinase B/Akt target, the transcription factor Trachealess. ..
  48. Morris S, Coogan C, Chamseddin K, Fernandez Kim S, Kolli S, Keller J, et al. Development of diet-induced insulin resistance in adult Drosophila melanogaster. Biochim Biophys Acta. 2012;1822:1230-7 pubmed publisher
    ..Therefore, the fly system may be a useful alternative tool in the investigation of molecular mechanisms of insulin resistance and the development of pharmacologic treatment options. ..
  49. Dickson B. Development. Wiring the brain with insulin. Science. 2003;300:440-1 pubmed
  50. Albert S, Twardzik T, Heisenberg M, Schneuwly S. Isolation and characterization of the droPIK57 gene encoding a new regulatory subunit of phosphatidylinositol 3-kinase from Drosophila melanogaster. Gene. 1997;198:181-9 pubmed
    ..We have cloned a gene for a regulatory subunit from Drosophila melanogaster, named droPIK57, from head-specific cDNA libraries...
  51. Coelho C, Leevers S. Do growth and cell division rates determine cell size in multicellular organisms?. J Cell Sci. 2000;113 ( Pt 17):2927-34 pubmed
    ..These interactions may provide a means of coordinating growth and cell division, such that cells divide only when they are above a minimum size. ..
  52. 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
  53. Begun D, Holloway A, Stevens K, Hillier L, Poh Y, Hahn M, et al. Population genomics: whole-genome analysis of polymorphism and divergence in Drosophila simulans. PLoS Biol. 2007;5:e310 pubmed
    ..simulans. ..
  54. Xi X, Tatei K, Kihara Y, Izumi T. Expression pattern of class I phosphoinositide 3-kinase and distribution of its product, phosphatidylinositol-3,4,5-trisphosphate, during Drosophila embryogenesis. Gene Expr Patterns. 2014;15:88-95 pubmed publisher
    ..We found that the RNA of Pi3K21B, encoding the Drosophila p60 regulatory subunit of the class I PI3Ks, was expressed maternally and expressed ..
  55. Leevers S. Perspectives: cell biology. All creatures great and small. Science. 1999;285:2082-3 pubmed
  56. 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...
  57. Jagut M, Mihaila Bodart L, Molla Herman A, Alin M, Lepesant J, Huynh J. A mosaic genetic screen for genes involved in the early steps of Drosophila oogenesis. G3 (Bethesda). 2013;3:409-25 pubmed publisher
    ..This collection of mutants will be useful to investigate further the early steps of Drosophila oogenesis at a genetic level. ..
  58. Martín Castellanos C, Edgar B. A characterization of the effects of Dpp signaling on cell growth and proliferation in the Drosophila wing. Development. 2002;129:1003-13 pubmed
    ..by Tkv(Q253D) was blocked by the cell cycle inhibitor RBF, and required normal activity of the growth effector, PI3K. Among the known Dpp targets, vestigial was the only one tested that was required for Tkv(Q253D)-induced growth...
  59. Clancy D, Gems D, Harshman L, Oldham S, Stocker H, Hafen E, et al. Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein. Science. 2001;292:104-6 pubmed
    ..The dwarf phenotype of chico homozygotes was also unnecessary for extension of life-span. The role of insulin/IGF signaling in regulating animal aging is therefore evolutionarily conserved. ..
  60. Alvarez Ponce D, Guirao Rico S, Orengo D, Segarra C, Rozas J, Aguade M. Molecular population genetics of the insulin/TOR signal transduction pathway: a network-level analysis in Drosophila melanogaster. Mol Biol Evol. 2012;29:123-32 pubmed publisher
    ..The detected polarity would be, therefore, intrinsic to the IT pathway architecture and function. ..
  61. 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 pubmed
    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...
  62. Jin J, Anthopoulos N, Wetsch B, Binari R, Isaac D, Andrew D, et al. Regulation of Drosophila tracheal system development by protein kinase B. Dev Cell. 2001;1:817-27 pubmed
    ..Using a combination of biochemical and transgenic approaches, we show that direct phosphorylation of Trh by PKB at serine 665 is essential for nuclear localization and functional activation of this regulator of branching morphogenesis. ..
  63. Shiojima I, Walsh K. Regulation of cardiac growth and coronary angiogenesis by the Akt/PKB signaling pathway. Genes Dev. 2006;20:3347-65 pubmed
    ..How this signaling pathway contributes to the development of physiological/pathological hypertrophy and heart failure will also be discussed. ..