Pdk1

Summary

Gene Symbol: Pdk1
Description: Phosphoinositide-dependent kinase 1
Alias: 1210, CG1201, CG1210, DSTPK61, Dmel\CG1210, Dstpk61, PDK, PDK-1, PDK1, PDK1/Pk61C, PK61C, Pk61C, Pk61C/PDK1, Pk61C, PDK1, Pk61c/PDK1, dPDK, dPDK-1, dPDK1, dSTPK61, pdk1, pk61c, Phosphoinositide-dependent kinase 1, CG1210-PA, CG1210-PB, CG1210-PC, CG1210-PD, CG1210-PE, CG1210-PF, CG1210-PG, CG1210-PH, CG1210-PJ, Pdk1-PA, Pdk1-PB, Pdk1-PC, Pdk1-PD, Pdk1-PE, Pdk1-PF, Pdk1-PG, Pdk1-PH, Pdk1-PJ, phosphoinositide dependent kinase 1, phosphoinositide-dependent kinase 1, pk61c, protein kinase 61C, serine/threonine protein kinase
Species: fruit fly

Top Publications

  1. Alessi D, Deak M, Casamayor A, Caudwell F, Morrice N, Norman D, et al. 3-Phosphoinositide-dependent protein kinase-1 (PDK1): structural and functional homology with the Drosophila DSTPK61 kinase. Curr Biol. 1997;7:776-89 pubmed
    ..3 and is expressed ubiquitously in human tissues. Human PDK1 is homologous to the Drosophila protein kinase DSTPK61, which has been implicated in the regulation of sex differentiation, oogenesis and spermatogenesis...
  2. 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. ..
  3. Reiling J, Doepfner K, Hafen E, Stocker H. Diet-dependent effects of the Drosophila Mnk1/Mnk2 homolog Lk6 on growth via eIF4E. Curr Biol. 2005;15:24-30 pubmed
    ..Overexpression of Lk6 also results in growth inhibition in an eIF4E-dependent manner. We propose a model of eIF4E regulation that may reconcile the contradictory findings with regard to the role of phosphorylation by Mnk1/2. ..
  4. Cho K, Lee J, Kim S, Kim D, Koh H, Lee J, et al. Drosophila phosphoinositide-dependent kinase-1 regulates apoptosis and growth via the phosphoinositide 3-kinase-dependent signaling pathway. Proc Natl Acad Sci U S A. 2001;98:6144-9 pubmed
    ..Here, we have isolated Drosophila PDK-1 (dPDK-1) mutants and characterized the in vivo roles of the kinase...
  5. 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...
  6. 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
  7. 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. ..
  8. 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
    ..dS6K activity is dependent on the Drosophila homologue of the phosphoinositide-dependent protein kinase 1, dPDK1, demonstrating that both dPDK1, as well as dTOR, mediated dS6K activation is phosphatidylinositide-3,4,5-..
  9. 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
    ..a P-element insertion that decreased expression of the insulin signaling gene phosphoinositide-dependent kinase 1 (PDK1) Precise excision of the P-element insertion reverted PDK1 expression and ARLI to the same as control flies, ..

More Information

Publications57

  1. 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. ..
  2. Scott R, Juhasz G, Neufeld T. Direct induction of autophagy by Atg1 inhibits cell growth and induces apoptotic cell death. Curr Biol. 2007;17:1-11 pubmed
    ..Furthermore, this work identifies autophagy as a critical mechanism by which inhibition of TOR signaling leads to reduced cell growth. ..
  3. Rollmann S, Magwire M, Morgan T, Ozsoy E, Yamamoto A, Mackay T, et al. Pleiotropic fitness effects of the Tre1-Gr5a region in Drosophila melanogaster. Nat Genet. 2006;38:824-9 pubmed
    ..Transposon-induced sex-specific and sex-antagonistic effects further accentuate the complex influences that intergenic transposable elements can contribute to quantitative trait phenotypes. ..
  4. 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. ..
  5. 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. ..
  6. 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. ..
  7. 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...
  8. Tunstall N, Herr A, de Bruyne M, Warr C. A screen for genes expressed in the olfactory organs of Drosophila melanogaster identifies genes involved in olfactory behaviour. PLoS ONE. 2012;7:e35641 pubmed publisher
  9. 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 hypoxic ..
  10. 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
    ..Our observations suggest that TSC1/2 and Rheb have different effects on the activity of TORC1 and -2, further supporting the complexity of TOR regulation. ..
  11. 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. ..
  12. Papatheodorou I, Ziehm M, Wieser D, Alic N, Partridge L, Thornton J. Using answer set programming to integrate RNA expression with signalling pathway information to infer how mutations affect ageing. PLoS ONE. 2012;7:e50881 pubmed publisher
    ..Our methods are available in the web-service NetEffects: http://www.ebi.ac.uk/thornton-srv/software/NetEffects. ..
  13. Stephens L, Anderson K, Stokoe D, Erdjument Bromage H, Painter G, Holmes A, et al. Protein kinase B kinases that mediate phosphatidylinositol 3,4,5-trisphosphate-dependent activation of protein kinase B. Science. 1998;279:710-4 pubmed
  14. Innocenti P, Chenoweth S. Interspecific divergence of transcription networks along lines of genetic variance in Drosophila: dimensionality, evolvability, and constraint. Mol Biol Evol. 2013;30:1358-67 pubmed publisher
  15. Doherty J, Sheehan A, Bradshaw R, Fox A, Lu T, Freeman M. PI3K signaling and Stat92E converge to modulate glial responsiveness to axonal injury. PLoS Biol. 2014;12:e1001985 pubmed publisher
    ..We propose that Drosophila glia use this auto-regulatory loop as a mechanism to adjust their reactive state following injury. ..
  16. 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. ..
  17. MacDougall C, Clyde D, Wood T, Todman M, Harbison D, Bownes M. Sex-specific transcripts of the Dstpk61 serine/threonine kinase gene in Drosophila melanogaster. Eur J Biochem. 1999;262:456-66 pubmed
    We describe the characterization of several transcripts of the Drosophila serine/threonine protein kinase 61 (Dstpk61) gene. Dstpk61 produces at least four transcripts, including a 3.0-kb testis-specific transcript, a 4...
  18. 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
  19. Chen K, Lin G, Haelterman N, Ho T, Li T, Li Z, et al. Loss of Frataxin induces iron toxicity, sphingolipid synthesis, and Pdk1/Mef2 activation, leading to neurodegeneration. elife. 2016;5: pubmed publisher
    ..in turn induces sphingolipid synthesis and ectopically activates 3-phosphoinositide dependent protein kinase-1 (Pdk1) and myocyte enhancer factor-2 (Mef2)...
  20. Stra├čburger K, Tiebe M, Pinna F, Breuhahn K, Teleman A. Insulin/IGF signaling drives cell proliferation in part via Yorkie/YAP. Dev Biol. 2012;367:187-96 pubmed publisher
    ..Interestingly, we also find the converse--that Yorkie signaling activates components of the insulin/TOR pathway. In sum, this crosstalk between IIS and Yorkie leads to coordinated regulation of these two oncogenic pathways. ..
  21. Montagne J, Lecerf C, Parvy J, Bennion J, Radimerski T, Ruhf M, et al. The nuclear receptor DHR3 modulates dS6 kinase-dependent growth in Drosophila. PLoS Genet. 2010;6:e1000937 pubmed publisher
    ..These results provide the first molecular link between the dS6K pathway, critical in controlling nutrient-dependent growth, and that of DHR3, a major mediator of ecdysone signaling, which, acting together, coordinate metamorphosis. ..
  22. Clyde D, Bownes M. The Dstpk61 locus of Drosophila produces multiple transcripts and protein isoforms, suggesting it is involved in multiple signalling pathways. J Endocrinol. 2000;167:391-401 pubmed
    The Drosophila gene Dstpk61 encodes a serine threonine protein kinase homologous to human phosphoinositide-dependent protein kinase (PDK1), and also has homologues in S. cerevisiae, S. pombe, C. elegans, A. thaliana, mouse, and sheep...
  23. 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. ..
  24. 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. ..
  25. Claeys I, Simonet G, Poels J, Van Loy T, Vercammen L, De Loof A, et al. Insulin-related peptides and their conserved signal transduction pathway. Peptides. 2002;23:807-16 pubmed
  26. 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. ..
  27. 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. ..
  28. Yang Q, Inoki K, Ikenoue T, Guan K. Identification of Sin1 as an essential TORC2 component required for complex formation and kinase activity. Genes Dev. 2006;20:2820-32 pubmed
    ..These data demonstrate that Sin1 together with Rictor are key components of mTORC2 and play an essential role in Akt phosphorylation and signaling. ..
  29. Partridge L, Alic N, Bjedov I, Piper M. Ageing in Drosophila: the role of the insulin/Igf and TOR signalling network. Exp Gerontol. 2011;46:376-81 pubmed publisher
    ..Reduced IIS can act acutely to lower death rate, implying that it may ameliorate the effects of ageing-related damage, rather than preventing it. ..
  30. Cheng L, Locke C, Davis G. S6 kinase localizes to the presynaptic active zone and functions with PDK1 to control synapse development. J Cell Biol. 2011;194:921-35 pubmed publisher
    ..We then provide evidence that S6K functions downstream of presynaptic PDK1 to control synaptic bouton size, active zone number, and synaptic function without influencing presynaptic bouton ..
  31. Pallares Cartes C, Cakan Akdogan G, Teleman A. Tissue-specific coupling between insulin/IGF and TORC1 signaling via PRAS40 in Drosophila. Dev Cell. 2012;22:172-82 pubmed publisher
    ..Finally, this work sheds some light on the question of whether TORC1 activity is coupled to IIS in vivo. ..
  32. Shen J, Curtis C, Tavare S, Tower J. A screen of apoptosis and senescence regulatory genes for life span effects when over-expressed in Drosophila. Aging (Albany NY). 2009;1:191-211 pubmed
  33. Towers P, Sattelle D. A Drosophila melanogaster cell line (S2) facilitates post-genome functional analysis of receptors and ion channels. Bioessays. 2002;24:1066-73 pubmed
    ..In addition, many useful orthologues of human disease genes are emerging from the Drosophila genome and the study of their functions and interactions is another area for postgenome applications of S2 cell lines. ..
  34. 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
    ..Our finding that phosphatidylinositol 3-kinase/Akt signaling and 14-3-3 cooperate to modulate the neurotoxicity of ataxin-1 provides insight into SCA1 pathogenesis and identifies potential targets for therapeutic intervention. ..
  35. Yavari A, Nagaraj R, Owusu Ansah E, Folick A, Ngo K, Hillman T, et al. Role of lipid metabolism in smoothened derepression in hedgehog signaling. Dev Cell. 2010;19:54-65 pubmed publisher
    ..Taken together, our results suggest a model in which Ptc directly or indirectly functions to suppress the accumulation of PI4P. Binding of Hh to Ptc derepresses the levels of PI4P, which, in turn, promotes Smo activation. ..
  36. Kamakura M. Royalactin induces queen differentiation in honeybees. Nature. 2011;473:478-83 pubmed publisher
    ..These findings indicate that a specific factor in royal jelly, royalactin, drives queen development through an Egfr-mediated signalling pathway. ..
  37. Eddison M, Guarnieri D, Cheng L, Liu C, Moffat K, Davis G, et al. arouser reveals a role for synapse number in the regulation of ethanol sensitivity. Neuron. 2011;70:979-90 pubmed publisher
    ..We thus show that a developmental abnormality affecting synapse number and ethanol sensitivity is not permanent and can be reversed by manipulating the environment of the adult fly. ..
  38. Cully M, Genevet A, Warne P, Treins C, Liu T, Bastien J, et al. A role for p38 stress-activated protein kinase in regulation of cell growth via TORC1. Mol Cell Biol. 2010;30:481-95 pubmed publisher
    ..These data suggest that p38 is an important positive regulator of TORC1 in both mammalian and Drosophila systems in response to certain stresses and growth factors. ..
  39. Cao C, Liu Y, Lehmann M. Fork head controls the timing and tissue selectivity of steroid-induced developmental cell death. J Cell Biol. 2007;176:843-52 pubmed
    ..More generally, they suggest that cell identity factors like Fkh play a pivotal role in the normal control of developmental cell death. ..
  40. Tan K, Goh S, Minakhina S. Genetic screen for regulators of lymph gland homeostasis and hemocyte maturation in Drosophila. G3 (Bethesda). 2012;2:393-405 pubmed publisher
  41. Tikhmyanova N, Tulin A, Roegiers F, Golemis E. Dcas supports cell polarization and cell-cell adhesion complexes in development. PLoS ONE. 2010;5:e12369 pubmed publisher
    ..These results support an important role for Cas proteins in cell-cell adhesion signaling in development. ..
  42. 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. ..
  43. Wu Q, Brown M. Signaling and function of insulin-like peptides in insects. Annu Rev Entomol. 2006;51:1-24 pubmed
  44. 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. ..
  45. 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. ..
  46. Logan Garbisch T, Bortolazzo A, Luu P, Ford A, Do D, Khodabakhshi P, et al. Developmental ethanol exposure leads to dysregulation of lipid metabolism and oxidative stress in Drosophila. G3 (Bethesda). 2014;5:49-59 pubmed publisher
    ..These data suggest a previously uncharacterized mechanism by which ethanol causes the symptoms associated with FASD. ..
  47. Andrioli L, Vasisht V, Theodosopoulou E, Oberstein A, Small S. Anterior repression of a Drosophila stripe enhancer requires three position-specific mechanisms. Development. 2002;129:4931-40 pubmed
    ..These results suggest a common mechanism for preventing anterior activation of three different eve enhancers. ..
  48. 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. ..