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Gene Review

Pi3K21B  -  CG2699 gene product from transcript CG2699-RE

Drosophila melanogaster

Synonyms: CG2699, Dmel\CG2699, Dp60, PI(3)K, PI3K, ...
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Disease relevance of Pi3K21B

  • Our results raise the possibility that neurofibroma formation in individuals with neurofibromatosis might result in part from a Ras-PI3K-Akt-dependent inhibition of FOXO within Schwann cells [1].
  • In step mutant animals both cell size and cell number are reduced, resulting in decreased body size and body weight in larvae, pupae and adults. step acts upstream of PI(3)K and is required for the proper regulation of Akt and the transcription factor FOXO [2].
  • In contrast to the mild effects of removing HM site phosphorylation at normal levels of PI3K activity, loss of TORC2 activity strongly inhibited hyperplasia caused by elevated pathway activity, as in mutants of the tumor suppressor PTEN [3].
  • TRB3 expression is remarkably reduced in prostate cancer PC-3 cells after inhibition of PI 3-kinase [4].
  • We also report that PI3K controls the expression and localization of synaptic markers in human neuroblastoma cells, suggesting that PI3K synaptogenic activity is conserved in humans [5].

High impact information on Pi3K21B

  • eIF4E, the mRNA 5' cap-binding protein, is regulated by its binding protein (4E-BP), a downstream target of phosphatidylinositol-3-OH kinase [PI(3)K] signaling [6].
  • The Drosophila insulin receptor (dInR) regulates cell growth and proliferation through the dPI3K/dAkt pathway, which is conserved in metazoan organisms [7].
  • Thus, Dp110 integrates inputs from its phosphotyrosine-binding adaptor and Ras to achieve maximal PI(3)K signalling in specific biological situations [8].
  • The Drosophila class I PI(3)K, Dp110, is activated by nutrient-responsive insulin signalling and modulates growth, oogenesis and metabolism [8].
  • In contrast, using both laser ablation and a novel wounding assay that allows localized treatment with inhibitory drugs, we show that PI3K is essential for hemocyte chemotaxis toward wounds and that Pvf signals and PDGF/VEGF receptor expression are not required for this rapid chemotactic response [9].

Biological context of Pi3K21B

  • 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 [10].
  • CONCLUSIONS: We conclude that during imaginal disc development, Dp110 and p60 regulate cell size, cell number and organ size [10].
  • Analysis of the sequence of p60 shows that the amino acids responsible for the SH2 domain binding specificity in mammalian p85alpha are conserved and predicts that the inter-SH2 domain has a coiled-coil structure [11].
  • The complex was found in larvae, pupae, and adults, consistent with p60 functioning as the adaptor for Dp110 throughout the Drosophila life cycle [11].
  • RESULTS: Null mutations in Dp110 and p60 were generated and used to demonstrate that they are essential genes that are autonomously required for imaginal disc cells to achieve their normal adult size [10].

Anatomical context of Pi3K21B

  • Second, neither exogenous ecdysone nor overexpression of PTEN, a silencer of PI3K signaling, restored fusion of autophagosomes with lysosomes in the fat body of dor mutants [12].
  • In this study, we show that elevated signaling through PI3K and Akt can prevent developmentally controlled death in the salivary glands of the fruit fly [13].
  • We report here the cloning of a novel PI 3-kinase, p170, from cDNA of insulin-sensitive mouse 3T3-L1 adipocytes [14].
  • Thus DOCK180 contained a phosphoinositide-binding domain, as did the other guanine nucleotide exchange factors with a Dbl homology domain, and was translocated to the plasma membrane on the activation of PI-3K [15].
  • We show here that the levels of phosphoinositide 3 kinase (PI3K) regulate synapse number in both Drosophila larval motor neurons and adult brain projection neurons [5].

Associations of Pi3K21B with chemical compounds

  • p60 is an adaptor for the Drosophila phosphoinositide 3-kinase, Dp110 [11].
  • These data demonstrate that the kinase and adaptor properties of ILK function together, in a Pi3 kinase-dependent manner, to regulate integrin-mediated cell attachment and signal transduction [16].
  • TRB3 expression is furthermore controlled by nutrient supplies: Both the lack of glucose or amino acids results in a substantial increase in TRB3 protein levels in a PI 3-kinase-dependent manner [4].
  • Previous work in our laboratory has indicated that the steroid hormone ecdysone triggers programmed autophagy in the fat body of Drosophila larvae by downregulating the class I phosphoinositide 3-kinase (PI3K) pathway [17].

Other interactions of Pi3K21B

  • Our results indicate that Dp110 and p60 signalling can affect growth in multiple ways, which has important implications for the function of signalling through class I(A) PI 3-kinases [10].
  • Mutant dFOXO lacking dAkt phosphorylation sites no longer responds to insulin inhibition, remains in the nucleus, and is constitutively active. dFOXO activation in S2 cells induces growth arrest and activates two key players of the dInR/dPI3K/dAkt pathway: the translational regulator d4EBP and the dInR itself [7].
  • PTEN is an important regulator of phosphoinositide turnover that antagonizes the activity of PI3-kinase [18].


  1. Phosphatidylinositol 3-kinase and Akt nonautonomously promote perineurial glial growth in Drosophila peripheral nerves. Lavery, W., Hall, V., Yager, J.C., Rottgers, A., Wells, M.C., Stern, M. J. Neurosci. (2007) [Pubmed]
  2. The cytohesin Steppke is essential for insulin signalling in Drosophila. Fuss, B., Becker, T., Zinke, I., Hoch, M. Nature (2006) [Pubmed]
  3. Re-evaluating AKT regulation: role of TOR complex 2 in tissue growth. Hietakangas, V., Cohen, S.M. Genes Dev. (2007) [Pubmed]
  4. TRB3 is a PI 3-kinase dependent indicator for nutrient starvation. Schwarzer, R., Dames, S., Tondera, D., Klippel, A., Kaufmann, J. Cell. Signal. (2006) [Pubmed]
  5. Age-independent synaptogenesis by phosphoinositide 3 kinase. Mart??n-Pe??a, A., Acebes, A., Rodr??guez, J.R., Sorribes, A., de Polavieja, G.G., Fern??ndez-F??nez, P., Ferr??s, A. J. Neurosci. (2006) [Pubmed]
  6. Starvation and oxidative stress resistance in Drosophila are mediated through the eIF4E-binding protein, d4E-BP. Tettweiler, G., Miron, M., Jenkins, M., Sonenberg, N., Lasko, P.F. Genes Dev. (2005) [Pubmed]
  7. Control of cell number by Drosophila FOXO: downstream and feedback regulation of the insulin receptor pathway. Puig, O., Marr, M.T., Ruhf, M.L., Tjian, R. Genes Dev. (2003) [Pubmed]
  8. Input from Ras is required for maximal PI(3)K signalling in Drosophila. Orme, M.H., Alrubaie, S., Bradley, G.L., Walker, C.D., Leevers, S.J. Nat. Cell Biol. (2006) [Pubmed]
  9. Distinct mechanisms regulate hemocyte chemotaxis during development and wound healing in Drosophila melanogaster. Wood, W., Faria, C., Jacinto, A. J. Cell Biol. (2006) [Pubmed]
  10. Regulation of imaginal disc cell size, cell number and organ size by Drosophila class I(A) phosphoinositide 3-kinase and its adaptor. Weinkove, D., Neufeld, T.P., Twardzik, T., Waterfield, M.D., Leevers, S.J. Curr. Biol. (1999) [Pubmed]
  11. p60 is an adaptor for the Drosophila phosphoinositide 3-kinase, Dp110. Weinkove, D., Leevers, S.J., MacDougall, L.K., Waterfield, M.D. J. Biol. Chem. (1997) [Pubmed]
  12. A dual function for Deep orange in programmed autophagy in the Drosophila melanogaster fat body. Lindmo, K., Simonsen, A., Brech, A., Finley, K., Rusten, T.E., Stenmark, H. Exp. Cell Res. (2006) [Pubmed]
  13. FOXO-independent suppression of programmed cell death by the PI3K/Akt signaling pathway in Drosophila. Liu, Y., Lehmann, M. Dev. Genes Evol. (2006) [Pubmed]
  14. Mouse p170 is a novel phosphatidylinositol 3-kinase containing a C2 domain. Virbasius, J.V., Guilherme, A., Czech, M.P. J. Biol. Chem. (1996) [Pubmed]
  15. Membrane recruitment of DOCK180 by binding to PtdIns(3,4,5)P3. Kobayashi, S., Shirai, T., Kiyokawa, E., Mochizuki, N., Matsuda, M., Fukui, Y. Biochem. J. (2001) [Pubmed]
  16. Integration of cell attachment, cytoskeletal localization, and signaling by integrin-linked kinase (ILK), CH-ILKBP, and the tumor suppressor PTEN. Attwell, S., Mills, J., Troussard, A., Wu, C., Dedhar, S. Mol. Biol. Cell (2003) [Pubmed]
  17. How a RING finger protein and a steroid hormone control autophagy. Lindmo, K., Stenmark, H. Autophagy. (2006) [Pubmed]
  18. Direct association of Bazooka/PAR-3 with the lipid phosphatase PTEN reveals a link between the PAR/aPKC complex and phosphoinositide signaling. von Stein, W., Ramrath, A., Grimm, A., Müller-Borg, M., Wodarz, A. Development (2005) [Pubmed]
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