Akt1

Summary

Gene Symbol: Akt1
Description: Akt1
Alias: AKT, AKT/PKB, AKT1, Akt, Akt/PKB, Akt1, PKB, CG4006, D-Akt, DAKT1, DAKT1/PKB, DAkt, DAkt1, DPKB, DRAC-PK, DRAC-PK66, DRAC-PK85, Dakt, Dakt1, Dmel\CG4006, Dpkb, PKB, PKB/AKT, PKB/Akt, PKB/dAKT, RAC, RacPK, akt, akt1, dAKT, dAKT/dPKB, dAKT1, dAkt, dAkt/PKB, dAkt1, dPKB, dakt, dakt1, l(3)04226, l(3)89Bq, p-Akt, pAkt, Akt1, Akt kinase, Akt1-PA, Akt1-PB, Akt1-PC, Akt1-PD, Akt1-PE, CG4006-PA, CG4006-PB, CG4006-PC, CG4006-PD, CG4006-PE, dAkt kinase, protein kinase B, related to PKA to PKC protein kinases, related to the A and C kinases
Species: fruit fly
Products:     Akt1

Top Publications

  1. Cavaliere V, Donati A, Hsouna A, Hsu T, Gargiulo G. dAkt kinase controls follicle cell size during Drosophila oogenesis. Dev Dyn. 2005;232:845-54 pubmed
    The Drosophila Akt (dAkt) serine/threonine kinase is a component of the insulin receptor/PI3K signaling pathway that regulates cell growth...
  2. Radimerski T, Montagne J, Hemmings Mieszczak M, Thomas G. Lethality of Drosophila lacking TSC tumor suppressor function rescued by reducing dS6K signaling. Genes Dev. 2002;16:2627-32 pubmed
    ..Here, we show that absence of Drosophila Tsc1/2 leads to constitutive dS6K activation and inhibition of dPKB, the latter effect being relieved by loss of dS6K...
  3. Potter C, Xu T. Mechanisms of size control. Curr Opin Genet Dev. 2001;11:279-86 pubmed
    ..The mechanisms of organ size control could also be critical targets for evolutionary events or disease processes such as tumorigenesis. ..
  4. 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
    ..and in vivo analyses in the third instar wing imaginal disc, we studied the regulatory circuitries that define dAkt activation...
  5. Biteau B, Karpac J, Supoyo S, Degennaro M, Lehmann R, Jasper H. Lifespan extension by preserving proliferative homeostasis in Drosophila. PLoS Genet. 2010;6:e1001159 pubmed publisher
  6. Verdu J, Buratovich M, Wilder E, Birnbaum M. Cell-autonomous regulation of cell and organ growth in Drosophila by Akt/PKB. Nat Cell Biol. 1999;1:500-6 pubmed
    ..that genetic manipulation of the phosphoinositide-3-OH-kinase-dependent serine/threonine protein kinase Akt (protein kinase B) during development of the Drosophila imaginal disc affects cell and organ size in an autonomous manner...
  7. 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
    ..Growth inhibition is associated with a reduction in S6K but not PKB/Akt activity...
  8. Gupta A, Toscano S, Trivedi D, Jones D, Mathre S, Clarke J, et al. Phosphatidylinositol 5-phosphate 4-kinase (PIP4K) regulates TOR signaling and cell growth during Drosophila development. Proc Natl Acad Sci U S A. 2013;110:5963-8 pubmed publisher
    ..Together, these results define dPIP4K activity as a regulator of cell growth and TOR signaling during larval development. ..
  9. Porstmann T, Santos C, Griffiths B, Cully M, Wu M, Leevers S, et al. SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth. Cell Metab. 2008;8:224-36 pubmed publisher
    ..The PI3-kinase/Akt signaling pathway induces cell growth via activation of complex 1 of the target of rapamycin (TORC1)...

More Information

Publications85

  1. 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. ..
  2. Dong J, Pan D. Tsc2 is not a critical target of Akt during normal Drosophila development. Genes Dev. 2004;18:2479-84 pubmed
    ..It was reported that Akt, an essential component of the insulin pathway, stimulates growth by phosphorylating and inhibiting tuberous ..
  3. 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. ..
  4. Hietakangas V, Cohen S. Re-evaluating AKT regulation: role of TOR complex 2 in tissue growth. Genes Dev. 2007;21:632-7 pubmed
    Phosphatidylinositol-3-kinase (PI3K)/AKT signaling is essential for growth and metabolism and is elevated in many cancers...
  5. 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. ..
  6. Kaplan D, Zimmermann G, Suyama K, Meyer T, Scott M. A nucleostemin family GTPase, NS3, acts in serotonergic neurons to regulate insulin signaling and control body size. Genes Dev. 2008;22:1877-93 pubmed publisher
    ..Peripheral insulin pathway activation rescues the growth defects of ns3 mutants. The findings suggest that NS3 acts in serotonergic neurons to regulate insulin signaling and thus exert global growth control. ..
  7. 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
    ..We have studied Drosophila Akt (Dakt1) and have shown that it is also involved in the regulation of cell size...
  8. Demontis F, Perrimon N. Integration of Insulin receptor/Foxo signaling and dMyc activity during muscle growth regulates body size in Drosophila. Development. 2009;136:983-93 pubmed publisher
    ..Thus, maximal dMyc transcriptional activity depends on InR to control muscle mass, which in turn induces a systemic behavioral response to allocate body size and proportions. ..
  9. Manning B, Cantley L. Rheb fills a GAP between TSC and TOR. Trends Biochem Sci. 2003;28:573-6 pubmed
  10. Frias M, Thoreen C, Jaffe J, Schroder W, Sculley T, Carr S, et al. mSin1 is necessary for Akt/PKB phosphorylation, and its isoforms define three distinct mTORC2s. Curr Biol. 2006;16:1865-70 pubmed
    ..mTORC2 is a hydrophobic motif kinase for the cell-survival protein Akt/PKB and, here, we identify mSin1 as a component of mTORC2 but not mTORC1...
  11. 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. ..
  12. 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. ..
  13. 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
    ..Moreover, when the expression of the dPI3K target, dPKB (Drosophila protein kinase B), was decreased to undetectable levels, we found that insulin could no longer trigger dS6K activation...
  14. Buttrick G, Beaumont L, Leitch J, Yau C, Hughes J, Wakefield J. Akt regulates centrosome migration and spindle orientation in the early Drosophila melanogaster embryo. J Cell Biol. 2008;180:537-48 pubmed publisher
    ..Here we find that, in the Drosophila melanogaster early embryo, reduced levels of the protein kinase Akt result in incomplete centrosome migration around cortical nuclei, bent mitotic spindles, and loss of nuclei into ..
  15. 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. ..
  16. Bjedov I, Toivonen J, Kerr F, Slack C, Jacobson J, Foley A, et al. Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster. Cell Metab. 2010;11:35-46 pubmed publisher
    ..Rapamycin could increase life span of weak insulin/Igf signaling (IIS) pathway mutants and of flies with life span maximized by dietary restriction, indicating additional mechanisms. ..
  17. Birse R, Choi J, Reardon K, Rodriguez J, Graham S, Diop S, et al. High-fat-diet-induced obesity and heart dysfunction are regulated by the TOR pathway in Drosophila. Cell Metab. 2010;12:533-44 pubmed publisher
    ..We conclude that deregulation of insulin-TOR signaling due to a HFD is responsible for mediating the detrimental effects on metabolism and heart function. ..
  18. 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...
  19. Potter C, Huang H, Xu T. Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size. Cell. 2001;105:357-68 pubmed
    ..Genetic epistasis data are consistent with a model that Tsc1 and Tsc2 function together in the insulin signaling pathway...
  20. 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
    Deregulation of Akt/protein kinase B (PKB) is implicated in the pathogenesis of cancer and diabetes...
  21. Dong J, Feldmann G, Huang J, Wu S, Zhang N, Comerford S, et al. Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell. 2007;130:1120-33 pubmed
    ..These results uncover a universal size-control mechanism in metazoan. ..
  22. Marshall L, Rideout E, Grewal S. Nutrient/TOR-dependent regulation of RNA polymerase III controls tissue and organismal growth in Drosophila. EMBO J. 2012;31:1916-30 pubmed publisher
    ..Thus, stimulation of Pol III is a key downstream effector of TOR in the control of cellular and systemic growth. ..
  23. Na J, Musselman L, Pendse J, Baranski T, Bodmer R, Ocorr K, et al. A Drosophila model of high sugar diet-induced cardiomyopathy. PLoS Genet. 2013;9:e1003175 pubmed publisher
    ..Our data establish Drosophila as a useful system for exploring specific aspects of diet-induced heart dysfunction and emphasize enzymes within the hexosamine biosynthetic pathway as candidate therapeutic targets. ..
  24. 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. ..
  25. 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 insulin/IGF-activated AKT signaling pathway plays a crucial role in regulating tissue growth and metabolism in multicellular animals...
  26. Staveley B, Ruel L, Jin J, Stambolic V, Mastronardi F, Heitzler P, et al. Genetic analysis of protein kinase B (AKT) in Drosophila. Curr Biol. 1998;8:599-602 pubmed
    ..effects of Pl 3-kinase have been linked to its activation of the pleckstrin homology (PH)-domain-containing protein kinase B (PKB or AKT) [8]. PKB/AKT was identified from an oncogene, v-akt, found in a rodent T-cell lymphoma [9]...
  27. Pagliarini R, Xu T. A genetic screen in Drosophila for metastatic behavior. Science. 2003;302:1227-31 pubmed
    ..These findings suggest that the oncogenic background of tissues makes a distinct contribution toward metastatic development. ..
  28. 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. ..
  29. 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 Phosphatidylinositol-3 kinase/Protein Kinase B (PI3K/PKB) signaling pathway controls growth, metabolism, and lifespan in animals, and deregulation of its activity is associated with diabetes and cancer in humans...
  30. Lanet E, Gould A, Maurange C. Protection of neuronal diversity at the expense of neuronal numbers during nutrient restriction in the Drosophila visual system. Cell Rep. 2013;3:587-94 pubmed publisher
    ..These studies reveal an adaptive mechanism that helps to retain a functional visual system over a range of different brain sizes in the face of suboptimal nutrition. ..
  31. Robinson B, Huang J, Hong Y, Moberg K. Crumbs regulates Salvador/Warts/Hippo signaling in Drosophila via the FERM-domain protein Expanded. Curr Biol. 2010;20:582-90 pubmed publisher
  32. 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
    ..Expression of d4E-BP in the eye and wing together with PI(3)K or dAkt1, the serine/threonine kinase downstream of PI(3)K, resulted in suppression of the growth phenotype elicited by ..
  33. Igaki T, Pagliarini R, Xu T. Loss of cell polarity drives tumor growth and invasion through JNK activation in Drosophila. Curr Biol. 2006;16:1139-46 pubmed
    ..Similar oncogenic cooperation mediated through these evolutionarily conserved signaling pathways could contribute to human cancer progression. ..
  34. 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. ..
  35. Puig O, Marr M, Ruhf M, Tjian R. Control of cell number by Drosophila FOXO: downstream and feedback regulation of the insulin receptor pathway. Genes Dev. 2003;17:2006-20 pubmed
    The Drosophila insulin receptor (dInR) regulates cell growth and proliferation through the dPI3K/dAkt pathway, which is conserved in metazoan organisms...
  36. Ikeya T, Broughton S, Alic N, Grandison R, Partridge L. The endosymbiont Wolbachia increases insulin/IGF-like signalling in Drosophila. Proc Biol Sci. 2009;276:3799-807 pubmed publisher
    ..This effect of Wolbachia infection on IIS could have an evolutionary explanation, and has some implications for studies of IIS in Drosophila and other organisms that harbour endosymbionts. ..
  37. DiAngelo J, Bland M, Bambina S, Cherry S, Birnbaum M. The immune response attenuates growth and nutrient storage in Drosophila by reducing insulin signaling. Proc Natl Acad Sci U S A. 2009;106:20853-8 pubmed publisher
    ..These data suggest that communication between these two regulatory systems evolved as a means to divert energy in times of need from organismal growth to the acute requirement of combating infection...
  38. 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 pubmed
    ..phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P(3)); however, PI(3,4,5)P(3)-dependent activation of Drosophila Akt is suppressed specifically by one of three spliced forms, dPTEN3...
  39. 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. ..
  40. 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
  41. Wu Q, Brown M. Signaling and function of insulin-like peptides in insects. Annu Rev Entomol. 2006;51:1-24 pubmed
  42. Schleich S, Teleman A. Akt phosphorylates both Tsc1 and Tsc2 in Drosophila, but neither phosphorylation is required for normal animal growth. PLoS ONE. 2009;4:e6305 pubmed publisher
    b>Akt, an essential component of the insulin pathway, is a potent inducer of tissue growth. One of Akt's phosphorylation targets is Tsc2, an inhibitor of the anabolic kinase TOR...
  43. Kanao T, Venderova K, Park D, Unterman T, Lu B, Imai Y. Activation of FoxO by LRRK2 induces expression of proapoptotic proteins and alters survival of postmitotic dopaminergic neuron in Drosophila. Hum Mol Genet. 2010;19:3747-58 pubmed publisher
    ..These data suggest that the cell death molecules regulated by FoxO are key factors during the neurodegeneration in LRRK2-linked PD. ..
  44. 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
    ..Our study identifies two novel regulators of insulin signaling, miR-8/miR-200 and USH/FOG2, and suggests their roles in adolescent growth, aging, and cancer. ..
  45. Koike Kumagai M, Yasunaga K, Morikawa R, Kanamori T, Emoto K. The target of rapamycin complex 2 controls dendritic tiling of Drosophila sensory neurons through the Tricornered kinase signalling pathway. EMBO J. 2009;28:3879-92 pubmed publisher
    ..These findings suggest that TORC2 likely acts together with the Trc signalling pathway to regulate the dendritic tiling of class IV da neurons, and thus uncover the first neuronal function of TORC2 in vivo. ..
  46. 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 publisher
  47. Potter C, Pedraza L, Xu T. Akt regulates growth by directly phosphorylating Tsc2. Nat Cell Biol. 2002;4:658-65 pubmed
    The direct mechanism by which the serine/threonine kinase Akt (also known as protein kinase B (PKB)) regulates cell growth is unknown...
  48. 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
    ..we performed genetic interaction studies and identified components of the phosphatidylinositol 3-kinase (PI3K)/Akt-signaling pathway as specific modulators of DJ-1A RNAi-induced neurodegeneration...
  49. Hirabayashi S, Baranski T, Cagan R. Transformed Drosophila cells evade diet-mediated insulin resistance through wingless signaling. Cell. 2013;154:664-75 pubmed publisher
    ..By targeting multiple steps in this circuit with rationally applied drug combinations, we demonstrate the potential of combinatorial drug intervention to treat diet-enhanced malignant tumors. ..
  50. 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
  51. Lee S, Kim S, Lee J, Park J, Lee G, Kim Y, et al. ATG1, an autophagy regulator, inhibits cell growth by negatively regulating S6 kinase. EMBO Rep. 2007;8:360-5 pubmed
    ..Taken together, our genetic and biochemical results strongly indicate crosstalk between autophagy and cell growth regulation. ..
  52. Berry D, Baehrecke E. Growth arrest and autophagy are required for salivary gland cell degradation in Drosophila. Cell. 2007;131:1137-48 pubmed
  53. Gao T, Furnari F, Newton A. PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth. Mol Cell. 2005;18:13-24 pubmed
    Akt/protein kinase B critically regulates the balance between cell survival and apoptosis. Phosphorylation of Akt at two key sites, the activation loop and the hydrophobic motif, activates the kinase and promotes cell survival...
  54. Anselmo A, Bumeister R, Thomas J, White M. Critical contribution of linker proteins to Raf kinase activation. J Biol Chem. 2002;277:5940-3 pubmed
    ..CNK is required for membrane recruitment of Raf, while KSR is likely required to couple Raf to upstream kinases. These results demonstrate that CNK and KSR are integral components of the cellular machinery mediating Raf activation. ..
  55. Fuss B, Becker T, Zinke I, Hoch M. The cytohesin Steppke is essential for insulin signalling in Drosophila. Nature. 2006;444:945-8 pubmed
    ..kinase cascade that includes phosphatidylinositol-3-OH kinase (PI(3)K) and the serine-threonine protein kinase Akt. This study identifies a new component of insulin signalling in Drosophila, the steppke gene (step)...
  56. 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
    ..reduction in IIS activity as judged by the localization of a PIP(3) reporter and the phosphorylation of protein kinase B (PKB)...
  57. Dekanty A, Lavista Llanos S, Irisarri M, Oldham S, Wappner P. The insulin-PI3K/TOR pathway induces a HIF-dependent transcriptional response in Drosophila by promoting nuclear localization of HIF-alpha/Sima. J Cell Sci. 2005;118:5431-41 pubmed
    ..Overexpression of dAKT and dPDK1 in normoxic embryos provoked a major increase in Sima nuclear localization, mimicking the effect of a ..
  58. Ueishi S, Shimizu H, H Inoue Y. Male germline stem cell division and spermatocyte growth require insulin signaling in Drosophila. Cell Struct Funct. 2009;34:61-9 pubmed
  59. 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. ..
  60. Chen H, Fernandez Funez P, Acevedo S, Lam Y, Kaytor M, Fernandez M, et al. Interaction of Akt-phosphorylated ataxin-1 with 14-3-3 mediates neurodegeneration in spinocerebellar ataxia type 1. Cell. 2003;113:457-68 pubmed
    ..The association of ataxin-1 with 14-3-3 is regulated by Akt phosphorylation, and in a Drosophila model of SCA1, both 14-3-3 and Akt modulate neurodegeneration...
  61. Yang Q, Inoki K, Kim E, Guan K. TSC1/TSC2 and Rheb have different effects on TORC1 and TORC2 activity. Proc Natl Acad Sci U S A. 2006;103:6811-6 pubmed
    ..However, the function of Rheb in the TORC2 regulation has not been elucidated. By measuring Akt and S6K phosphorylation as a functional assay for TORC1 and -2, here, we report that dRheb has an inhibitory effect ..
  62. 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. ..
  63. 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 pathway to ..
  64. Coffman C, Wayne M, Nuzhdin S, Higgins L, McIntyre L. Identification of co-regulated transcripts affecting male body size in Drosophila. Genome Biol. 2005;6:R53 pubmed
    ..Applied to body size in Drosophila simulans, an evolutionarily important complex trait, a factor was directly associated with body size. ..
  65. Franke T, Tartof K, Tsichlis P. The SH2-like Akt homology (AH) domain of c-akt is present in multiple copies in the genome of vertebrate and invertebrate eucaryotes. Cloning and characterization of the Drosophila melanogaster c-akt homolog Dakt1. Oncogene. 1994;9:141-8 pubmed
    ..One of them was cloned, and found by sequence analysis, to define an Akt related gene (Dakt1). Comparison between the coding regions of c-akt and Dakt1 revealed 64.6% identity at the nucleotide level and 76...
  66. Martín Peña A, Acebes A, Rodriguez J, Sorribes A, de Polavieja G, Fernandez Funez P, et al. Age-independent synaptogenesis by phosphoinositide 3 kinase. J Neurosci. 2006;26:10199-208 pubmed
    ..Thus, we propose that PI3K stimulation can be applied to prevent or delay synapse loss in normal aging and in neurological disorders. ..
  67. 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
    Forkhead transcription factors belonging to the FOXO subfamily are negatively regulated by protein kinase B (PKB) in response to signaling by insulin and insulin-like growth factor in Caenorhabditis elegans and mammals...
  68. 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
    b>Protein kinase B (PKB, also termed Akt) is a phosphatidylinositol 3' kinase (PI3'K)-dependent enzyme implicated in survival signaling and human tumorigenesis...
  69. Luo X, Puig O, Hyun J, Bohmann D, Jasper H. Foxo and Fos regulate the decision between cell death and survival in response to UV irradiation. EMBO J. 2007;26:380-90 pubmed
    ..These data suggest that integrating stress and survival signals through Foxo drives the decision between cell death and repair of damaged cells in vivo. ..
  70. Lee K, Kwon O, Lee J, Kwon K, Min K, Jung S, et al. Drosophila short neuropeptide F signalling regulates growth by ERK-mediated insulin signalling. Nat Cell Biol. 2008;10:468-75 pubmed publisher
    ..The fat body of sNPF mutant Drosophila had downregulated Akt, nuclear localized FOXO, upregulated translational inhibitor 4E-BP and reduced cell size...
  71. 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. ..
  72. 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
    ..Here we show that, in Drosophila, dPDK1 controls cellular and organism growth by activating dAkt and S6 kinase, dS6K...
  73. Hennig K, Colombani J, Neufeld T. TOR coordinates bulk and targeted endocytosis in the Drosophila melanogaster fat body to regulate cell growth. J Cell Biol. 2006;173:963-74 pubmed
    ..Our data indicate that endocytosis acts both as an effector function downstream of TOR and as a physiologically relevant regulator of TOR signaling...
  74. Guo H, Zhong Y. Requirement of Akt to mediate long-term synaptic depression in Drosophila. J Neurosci. 2006;26:4004-14 pubmed
    ..mutants with defects in memory or signal transduction pathways, we found that LTD is strongly reduced in the akt mutants...
  75. Rera M, Clark R, Walker D. Intestinal barrier dysfunction links metabolic and inflammatory markers of aging to death in Drosophila. Proc Natl Acad Sci U S A. 2012;109:21528-33 pubmed publisher
    ..linked to aging, including impaired insulin/insulin-like growth factor signaling, as evidenced by a reduction in Akt activation and up-regulation of dFOXO target genes...
  76. 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
    ..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...