Genomes and Genes
Gene Symbol: Pten
Description: Phosphatase and tensin homolog
Alias: CG5671, DPTEN, Dmel\CG5671, PTEN, PTEN3, dPTEN, dPten, dpten, pten, phosphatase and tensin homolog, CG5671-PA, CG5671-PB, CG5671-PC, CG5671-PD, CG5671-PE, CG5671-PG, CG5671-PH, PI 3-phosphatase, PTEN, PtdIns(3,4,5)P3 phosphatase, Pten-PA, Pten-PB, Pten-PC, Pten-PD, Pten-PE, Pten-PG, Pten-PH, drosophila phosphatase and tensin homologue deleted on chromosome 10, phosphatase and tensin homologue, phosphatidylinositol (3,4,5)-trisphosphate phosphatase
Species: fruit fly
- 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..Here, we show that dPTEN, a Drosophila homolog of the mammalian PTEN tumor suppressor gene, plays an essential role in the control of cell ..
- 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. ..
- Saucedo L, Gao X, Chiarelli D, Li L, Pan D, Edgar B. Rheb promotes cell growth as a component of the insulin/TOR signalling network. Nat Cell Biol. 2003;5:566-71 pubmed..Levels of rheb mRNA are rapidly induced in response to protein starvation, and overexpressed Rheb can drive cell growth in starved animals, suggesting a role for Rheb in the nutritional control of cell growth. ..
- 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. ..
- 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
- Maehama T, Kosaka N, Okahara F, Takeuchi K, Umeda M, Dixon J, et al. Suppression of a phosphatidylinositol 3-kinase signal by a specific spliced variant of Drosophila PTEN. FEBS Lett. 2004;565:43-7 pubmedDrosophila PTEN (dPTEN) plays indispensable roles in the development of Drosophila melanogaster by controlling cell size and number...
- 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. ..
- Stocker H, Radimerski T, Schindelholz B, Wittwer F, Belawat P, Daram P, et al. Rheb is an essential regulator of S6K in controlling cell growth in Drosophila. Nat Cell Biol. 2003;5:559-65 pubmed
- Kim E, Goraksha Hicks P, Li L, Neufeld T, Guan K. Regulation of TORC1 by Rag GTPases in nutrient response. Nat Cell Biol. 2008;10:935-45 pubmed publisher..Genetic studies in Drosophila also show that Rag GTPases regulate cell growth, autophagy and animal viability during starvation. Our studies establish a function of Rag GTPases in TORC1 activation in response to amino acid signals. ..
- 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. ..
- Rhiner C, Diaz B, Portela M, Poyatos J, Fernández Ruíz I, López Gay J, et al. Persistent competition among stem cells and their daughters in the Drosophila ovary germline niche. Development. 2009;136:995-1006 pubmed publisher..Moreover, competitive interactions among stem cells may be relevant for the successful application of stem cell therapies in humans. ..
- Tsuda M, Kobayashi T, Matsuo T, Aigaki T. Insulin-degrading enzyme antagonizes insulin-dependent tissue growth and Abeta-induced neurotoxicity in Drosophila. FEBS Lett. 2010;584:2916-20 pubmed publisher..Using dIde(KO) as a model, further investigations into the biological functions of IDE and its role in the pathogenesis of DM2 and AD can be made...
- Kim R, Peters M, Jang Y, Shi W, Pintilie M, Fletcher G, et al. DJ-1, a novel regulator of the tumor suppressor PTEN. Cancer Cell. 2005;7:263-73 pubmedThe phosphatidylinositol 3' kinase (PI3'K) pathway, which regulates cell survival, is antagonized by the PTEN tumor suppressor. The regulation of PTEN is unclear...
- 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..Thus, in cells lacking TOR, autophagy plays a protective role that is dominant over its potential role as a growth suppressor. ..
- Nuzhdin S, Brisson J, Pickering A, Wayne M, Harshman L, McIntyre L. Natural genetic variation in transcriptome reflects network structure inferred with major effect mutations: insulin/TOR and associated phenotypes in Drosophila melanogaster. BMC Genomics. 2009;10:124 pubmed publisher..In summary, our results question the assertion of the 'sparse' nature of genetic networks, while validating and extending candidate gene approaches in the analyses of complex traits. ..
- 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..This mechanism indicates that dietary nutrients and remote organs, as well as local niches, are key regulators of transitions in stem-cell behaviour...
- 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. ..
- 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..Finally, we demonstrate that blocking the expression of Drosophila PTEN results in the activation of DAKT...
- Hwangbo D, Gershman B, Gersham B, Tu M, Palmer M, Tatar M. Drosophila dFOXO controls lifespan and regulates insulin signalling in brain and fat body. Nature. 2004;429:562-6 pubmed..These findings suggest that autonomous and non-autonomous roles of insulin signalling combine to control ageing. ..
- 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..Hence, these studies link hormonal induction of autophagy to the regulatory function of the PI3K signaling pathway in vivo. ..
- 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. ..
- 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. ..
- 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..The insulin-induced activations of dERK and dAKT were blocked by LY294002, dPTEN, and by an AKT inhibitor, indicating involvement of dPI3K and dAKT in the insulin-induced dERK and dAKT ..
- Bateman J, McNeill H. Temporal control of differentiation by the insulin receptor/tor pathway in Drosophila. Cell. 2004;119:87-96 pubmed..Examination of InR, PI3K, PTEN, Tor, Rheb, and S6 kinase mutants demonstrates that increased InR signaling leads to precocious differentiation ..
- Tapon N, Ito N, Dickson B, Treisman J, Hariharan I. The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation. Cell. 2001;105:345-55 pubmed..In postmitotic mutant cells, levels of Cyclin E and Cyclin A are elevated. This correlates with a tendency for these cells to reenter the cell cycle inappropriately as is observed in the human lesions. ..
- Lizcano J, Alrubaie S, Kieloch A, Deak M, Leevers S, Alessi D. Insulin-induced Drosophila S6 kinase activation requires phosphoinositide 3-kinase and protein kinase B. Biochem J. 2003;374:297-306 pubmed..to decrease expression of dPI3K and the PtdIns(3,4,5) P (3) phosphatase dPTEN ( Drosophila phosphatase and tensin homologue deleted on chromosome 10) in Kc167 and S2 cells...
- Sarbassov D, Guertin D, Ali S, Sabatini D. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science. 2005;307:1098-101 pubmed..Rictor-mTOR may serve as a drug target in tumors that have lost the expression of PTEN, a tumor suppressor that opposes Akt/PKB activation.
- Zhang H, Stallock J, Ng J, Reinhard C, Neufeld T. Regulation of cellular growth by the Drosophila target of rapamycin dTOR. Genes Dev. 2000;14:2712-24 pubmed..Our results suggest that dTOR regulates growth during animal development by coupling growth factor signaling to nutrient availability. ..
- 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..Furthermore, chico; lnk double mutants are synthetically lethal, suggesting that Chico and Lnk fulfill independent but partially redundant functions in the activation of PI3K upon InR stimulation. ..
- 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..The effect of insulin signaling upon TOR activity varies according to cellular type and context. ..
- Chen F, Archambault V, Kar A, Lio P, D Avino P, Sinka R, et al. Multiple protein phosphatases are required for mitosis in Drosophila. Curr Biol. 2007;17:293-303 pubmed..Discovery of several novel cell-cycle PPs identifies a need for further studies of protein dephosphorylation. ..
- Howlett E, Lin C, Lavery W, Stern M. A PI3-kinase-mediated negative feedback regulates neuronal excitability. PLoS Genet. 2008;4:e1000277 pubmed publisher..Our work suggests that some of the deficits in these neurological disorders might result from disruption of glutamate-mediated homeostasis of neuronal excitability. ..
- 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..Furthermore, we present biochemical and genetic evidence that loss of the homolog of the tumor suppressor gene, Pten, results in increased PtdInsP(3) levels and that these increased levels are sufficient to compensate for the ..
- 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...
- Knox S, Ge H, Dimitroff B, Ren Y, Howe K, Arsham A, et al. Mechanisms of TSC-mediated control of synapse assembly and axon guidance. PLoS ONE. 2007;2:e375 pubmed
- Gutierrez E, Wiggins D, Fielding B, Gould A. Specialized hepatocyte-like cells regulate Drosophila lipid metabolism. Nature. 2007;445:275-80 pubmed..These findings provide evidence that some lipid-processing functions of the mammalian liver are performed in insects by oenocytes...
- Gingras A, Raught B, Sonenberg N. Regulation of translation initiation by FRAP/mTOR. Genes Dev. 2001;15:807-26 pubmed
- Shingleton A. Body-size regulation: combining genetics and physiology. Curr Biol. 2005;15:R825-7 pubmed..New research has revealed that the activity of the insulin-signaling pathway in the prothoracic gland of Drosophila modulates ecdysone release and thereby influences both the duration and rate of larval growth. ..
- 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..The fact that Susi is expressed in a circadian rhythm, with highest levels during the night, suggests that Susi attenuates insulin signaling during the fasting period. ..
- 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. ..
- Tang H, Smith Caldas M, Driscoll M, Salhadar S, Shingleton A. FOXO regulates organ-specific phenotypic plasticity in Drosophila. PLoS Genet. 2011;7:e1002373 pubmed publisher..These data indicate that the extent of phenotypic plasticity may be modified by changes in the expression of genes involved in signaling environmental information to developmental processes. ..
- Wessells R, Fitzgerald E, Cypser J, Tatar M, Bodmer R. Insulin regulation of heart function in aging fruit flies. Nat Genet. 2004;36:1275-81 pubmed..Moreover, interfering with InR signaling exclusively in the heart, by overexpressing the phosphatase dPTEN or the forkhead transcription factor dFOXO, prevents the decline in cardiac performance with age...
- Gao X, Zhang Y, Arrazola P, Hino O, Kobayashi T, Yeung R, et al. Tsc tumour suppressor proteins antagonize amino-acid-TOR signalling. Nat Cell Biol. 2002;4:699-704 pubmed..Our studies identify Tsc1 and Tsc2 as regulators of the amino acid-TOR pathway and provide a new paradigm for how proteins involved in nutrient sensing function as tumour suppressors. ..
- Yang Y, Gehrke S, Haque M, Imai Y, Kosek J, Yang L, et al. Inactivation of Drosophila DJ-1 leads to impairments of oxidative stress response and phosphatidylinositol 3-kinase/Akt signaling. Proc Natl Acad Sci U S A. 2005;102:13670-5 pubmed..Manipulation of PI3K/Akt signaling may therefore offer therapeutic benefits for the treatment of PD. ..
- 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..by phosphatidylinositol 3-OH kinase (PI3'K) signaling and has shown to be hyperactivated through the loss of the PTEN tumor suppressor...
- Gao X, Pan D. TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth. Genes Dev. 2001;15:1383-92 pubmed..Taken together, our studies identified the TSC tumor suppressors as novel negative regulators of insulin signaling. ..
- 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..Surprisingly, RNAi of dAkt also affected insulin-stimulated phosphorylation of dS6K, indicating that dAkt may also play a role in dS6K phosphorylation. ..
- 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 pubmedMutations in the tumor suppressor gene PTEN (MMAC1/TEP1) are associated with a large number of human cancers and several autosomal-dominant disorders...
- 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..Thus, the results suggest that dPDK1 is required for dRSK but not dPKN activation and that it regulates insulin-mediated growth through two main effector branches, dAkt and dS6K. ..
- Raisin S, Pantalacci S, Breittmayer J, Leopold P. A new genetic locus controlling growth and proliferation in Drosophila melanogaster. Genetics. 2003;164:1015-25 pubmed..This suggested either that a particular combination of these transcripts was necessary or that other sequences are involved. ..
- Geminard C, Rulifson E, Leopold P. Remote control of insulin secretion by fat cells in Drosophila. Cell Metab. 2009;10:199-207 pubmed publisher..Thus, the availability of nutrients is remotely sensed in fat body cells and conveyed to the brain IPCs by a humoral signal controlling ILP release. ..
- Prober D, Edgar B. Interactions between Ras1, dMyc, and dPI3K signaling in the developing Drosophila wing. Genes Dev. 2002;16:2286-99 pubmed
- 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..Here we show that the highly evolutionarily conserved Drosophila PTEN homolog, DPTEN, suppresses hyperplastic growth in flies by reducing cell size and number...