KEGG   PATHWAY: pvt04068
Entry
pvt04068                    Pathway                                
Name
FoxO signaling pathway - Pogona vitticeps (central bearded dragon)
Description
The forkhead box O (FOXO) family of transcription factors regulates the expression of genes in cellular physiological events including apoptosis, cell-cycle control, glucose metabolism, oxidative stress resistance, and longevity. A central regulatory mechanism of FOXO proteins is phosphorylation by the serine-threonine kinase Akt/protein kinase B (Akt/PKB), downstream of phosphatidylinositol 3-kinase (PI3K), in response to insulin or several growth factors. Phosphorylation at three conserved residues results in the export of FOXO proteins from the nucleus to the cytoplasm, thereby decreasing expression of FOXO target genes. In contrast, the stress-activated c-Jun N-terminal kinase (JNK) and the energy sensing AMP-activated protein kinase (AMPK), upon oxidative and nutrient stress stimuli phosphorylate and activate FoxOs. Aside from PKB, JNK and AMPK, FOXOs are regulated by multiple players through several post-translational modifications, including phosphorylation, but also acetylation, methylation and ubiquitylation.
Class
Environmental Information Processing; Signal transduction
Pathway map
pvt04068  FoxO signaling pathway
pvt04068

Other DBs
GO: 0009267
Organism
Pogona vitticeps (central bearded dragon) [GN:pvt]
Gene
110088538  TGFB1; transforming growth factor beta-1 [KO:K13375]
110087066  TGFB2; transforming growth factor beta-2 [KO:K13376]
110083352  transforming growth factor beta-2-like [KO:K13376]
110079121  TGFB3; transforming growth factor beta-3 isoform X1 [KO:K13377]
110086076  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
110090113  TGF-beta receptor type-2-like [KO:K04388] [EC:2.7.11.30]
110086832  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
110088492  mothers against decapentaplegic homolog 4-like [KO:K04501]
110088634  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
110079304  STK11; serine/threonine-protein kinase STK11 isoform X1 [KO:K07298] [EC:2.7.11.1]
110073913  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
110077130  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
110088958  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
110089841  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
110074862  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
110078204  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200]
110071918  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
110088439  NLK; serine/threonine-protein kinase NLK [KO:K04468] [EC:2.7.11.24]
110081806  serine/threonine-protein kinase NLK2-like isoform X1 [KO:K04468] [EC:2.7.11.24]
110080059  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
110075109  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
110073660  SETD7; histone-lysine N-methyltransferase SETD7 isoform X1 [KO:K11431] [EC:2.1.1.364]
110089145  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
110076024  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
110087595  SIRT1; NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
110090438  USP7; ubiquitin carboxyl-terminal hydrolase 7 [KO:K11838] [EC:3.4.19.12]
110082351  SLC2A4; solute carrier family 2, facilitated glucose transporter member 4 isoform X1 [KO:K07191]
110087777  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
110073473  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
110085327  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
110076762  STK4; serine/threonine-protein kinase 4 isoform X1 [KO:K04411]
110084792  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
110072986  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
110076559  INS; insulin [KO:K04526]
110072679  INSR; insulin receptor [KO:K04527] [EC:2.7.10.1]
110078456  IRS1; insulin receptor substrate 1 [KO:K16172]
110082325  insulin receptor substrate 1-like [KO:K16172]
110074287  IRS4; insulin receptor substrate 4 [KO:K07187]
110090941  IRS2; insulin receptor substrate 2 [KO:K07187]
110081909  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110078719  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
110073252  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110082359  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
110073778  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
110072561  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
110073951  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
110085010  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
110087236  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
110072148  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
110083120  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN isoform X1 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
110090951  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110075943  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110075706  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110071906  SGK1; serine/threonine-protein kinase Sgk1 isoform X1 [KO:K13302] [EC:2.7.11.1]
110083029  SGK2; serine/threonine-protein kinase Sgk2 isoform X1 [KO:K13303] [EC:2.7.11.1]
110089237  serine/threonine-protein kinase Sgk3 isoform X1 [KO:K13304] [EC:2.7.11.1]
110076126  FOXO1; forkhead box protein O1 [KO:K07201]
110083133  FOXO3; forkhead box protein O3 [KO:K09408]
110080186  FOXO4; forkhead box protein O4 [KO:K12358]
110085624  FOXO6; forkhead box protein O6 [KO:K17847]
110088369  GRM1; metabotropic glutamate receptor 1 isoform X1 [KO:K04603]
110073958  HOMER1; homer protein homolog 1 isoform X1 [KO:K15010]
110077275  HOMER2; homer protein homolog 2 [KO:K15010]
110072538  HOMER3; homer protein homolog 3 isoform X1 [KO:K15010]
110074388  AGAP2; arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 isoform X1 [KO:K17848]
110075947  CSNK1E; casein kinase I [KO:K08960] [EC:2.7.11.1]
110073207  IL6; interleukin-6 [KO:K05405]
110088413  IL10; interleukin-10 isoform X1 [KO:K05443]
110074829  STAT3; signal transducer and activator of transcription 3 [KO:K04692]
110087292  EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
110081594  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
110085805  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
110089155  SOS2; son of sevenless homolog 2 [KO:K03099]
110079544  SOS1; son of sevenless homolog 1 [KO:K03099]
110074175  HRAS; GTPase HRas [KO:K02833]
110082993  KRAS; GTPase KRas isoform X1 [KO:K07827]
110078528  GTPase HRas-like [KO:K07827]
110072322  NRAS; GTPase NRas isoform X1 [KO:K07828]
110082693  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
110083799  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
110081172  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
110085468  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
110072466  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
110081803  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
110088651  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
110089644  mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
110089645  mitogen-activated protein kinase 12-like isoform X1 [KO:K04441] [EC:2.7.11.24]
110079793  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
110079814  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
110073535  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
110078497  PRMT1; protein arginine N-methyltransferase 1 isoform X1 [KO:K11434] [EC:2.1.1.319]
110075648  forkhead box protein G1-like [KO:K09385]
110076372  FOXG1; LOW QUALITY PROTEIN: forkhead box protein G1 [KO:K09385]
110073972  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
110074534  CCNB2; G2/mitotic-specific cyclin-B2 isoform X1 [KO:K21770]
110080169  CCNB3; G2/mitotic-specific cyclin-B3 [KO:K21771]
110073542  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
110085249  CCNG2; cyclin-G2 [KO:K10146]
110077364  cyclin-dependent kinase 4 inhibitor B-like [KO:K04685]
110077365  cyclin-dependent kinase 4 inhibitor B-like [KO:K04685]
110077984  CDKN2D; cyclin-dependent kinase 4 inhibitor D isoform X1 [KO:K06623]
110079972  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
110075002  cyclin-dependent kinase inhibitor 1-like [KO:K06625]
110074986  cyclin-dependent kinase inhibitor 1B-like [KO:K06624]
110082483  RBL2; retinoblastoma-like protein 2 [KO:K16332]
110084996  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
110088668  PLK2; serine/threonine-protein kinase PLK2 [KO:K08861] [EC:2.7.11.21]
110073767  PLK3; serine/threonine-protein kinase PLK3 [KO:K08862] [EC:2.7.11.21]
110072845  PLK4; serine/threonine-protein kinase PLK4 isoform X1 [KO:K08863] [EC:2.7.11.21]
110079870  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
110080579  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
110072507  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
110089831  FASLG; tumor necrosis factor ligand superfamily member 6 isoform X1 [KO:K04389]
110087021  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
110079056  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
110091624  BCL6; B-cell lymphoma 6 protein [KO:K15618]
110075154  BNIP3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464]
110079832  BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like isoform X1 [KO:K15464]
110072048  ATG12; ubiquitin-like protein ATG12 isoform X1 [KO:K08336]
110076328  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
110090845  gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
110082372  GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
110073526  CAT; catalase isoform X1 [KO:K03781] [EC:1.11.1.6]
110087569  SOD2; superoxide dismutase [Mn], mitochondrial [KO:K04564] [EC:1.15.1.1]
110084084  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
110081096  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] isoform X1 [KO:K01596] [EC:4.1.1.32]
110087540  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
110076912  G6PC2; glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
110080299  glucose-6-phosphatase-like [KO:K01084] [EC:3.1.3.9]
110080313  glucose-6-phosphatase-like isoform X1 [KO:K01084] [EC:3.1.3.9]
110079146  G6PC3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
110080088  IL7R; interleukin-7 receptor subunit alpha isoform X1 [KO:K05072]
110076502  S1PR1; sphingosine 1-phosphate receptor 1 [KO:K04288]
110079311  S1PR4; sphingosine 1-phosphate receptor 4 [KO:K04293]
110090247  RAG1; V(D)J recombination-activating protein 1 [KO:K10628] [EC:2.3.2.27]
110090248  RAG2; V(D)J recombination-activating protein 2 [KO:K10988]
110080561  FBXO32; F-box only protein 32 isoform X1 [KO:K10305]
110073428  FBXO25; F-box only protein 25 isoform X1 [KO:K10305]
Compound
C00008  ADP
C00020  AMP
C00025  L-Glutamate
C00031  D-Glucose
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
  Authors
Glauser DA, Schlegel W
  Title
The emerging role of FOXO transcription factors in pancreatic beta cells.
  Journal
J Endocrinol 193:195-207 (2007)
DOI:10.1677/JOE-06-0191
Reference
  Authors
van der Horst A, Burgering BM
  Title
Stressing the role of FoxO proteins in lifespan and disease.
  Journal
Nat Rev Mol Cell Biol 8:440-50 (2007)
DOI:10.1038/nrm2190
Reference
  Authors
Zhang X, Tang N, Hadden TJ, Rishi AK
  Title
Akt, FoxO and regulation of apoptosis.
  Journal
Biochim Biophys Acta 1813:1978-86 (2011)
DOI:10.1016/j.bbamcr.2011.03.010
Reference
  Authors
Eijkelenboom A, Burgering BM
  Title
FOXOs: signalling integrators for homeostasis maintenance.
  Journal
Nat Rev Mol Cell Biol 14:83-97 (2013)
DOI:10.1038/nrm3507
Reference
  Authors
Daitoku H, Fukamizu A
  Title
FOXO transcription factors in the regulatory networks of longevity.
  Journal
J Biochem 141:769-74 (2007)
DOI:10.1093/jb/mvm104
Reference
  Authors
Hedrick SM
  Title
The cunning little vixen: Foxo and the cycle of life and death.
  Journal
Nat Immunol 10:1057-63 (2009)
DOI:10.1038/ni.1784
Reference
  Authors
Coffer PJ, Burgering BM
  Title
Forkhead-box transcription factors and their role in the immune system.
  Journal
Nat Rev Immunol 4:889-99 (2004)
DOI:10.1038/nri1488
Reference
  Authors
Ro SH, Liu D, Yeo H, Paik JH
  Title
FoxOs in neural stem cell fate decision.
  Journal
Arch Biochem Biophys 534:55-63 (2013)
DOI:10.1016/j.abb.2012.07.017
Reference
  Authors
Maiese K, Chong ZZ, Shang YC
  Title
OutFOXOing disease and disability: the therapeutic potential of targeting FoxO proteins.
  Journal
Trends Mol Med 14:219-27 (2008)
DOI:10.1016/j.molmed.2008.03.002
Reference
  Authors
Hagenbuchner J, Ausserlechner MJ
  Title
Mitochondria and FOXO3: breath or die.
  Journal
Front Physiol 4:147 (2013)
DOI:10.3389/fphys.2013.00147
Reference
  Authors
Maiese K, Chong ZZ, Shang YC
  Title
"Sly as a FOXO": new paths with Forkhead signaling in the brain.
  Journal
Curr Neurovasc Res 4:295-302 (2007)
DOI:10.2174/156720207782446306
Reference
  Authors
Oh HM, Yu CR, Dambuza I, Marrero B, Egwuagu CE
  Title
STAT3 protein interacts with Class O Forkhead transcription factors in the cytoplasm and regulates nuclear/cytoplasmic localization of FoxO1 and FoxO3a proteins in CD4(+) T cells.
  Journal
J Biol Chem 287:30436-43 (2012)
DOI:10.1074/jbc.M112.359661
Reference
  Authors
Huang H, Tindall DJ
  Title
Regulation of FOXO protein stability via ubiquitination and proteasome degradation.
  Journal
Biochim Biophys Acta 1813:1961-4 (2011)
DOI:10.1016/j.bbamcr.2011.01.007
Reference
  Authors
Greer EL, Brunet A
  Title
FOXO transcription factors at the interface between longevity and tumor suppression.
  Journal
Oncogene 24:7410-25 (2005)
DOI:10.1038/sj.onc.1209086
Reference
  Authors
Seoane J, Le HV, Shen L, Anderson SA, Massague J
  Title
Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation.
  Journal
Cell 117:211-23 (2004)
DOI:10.1016/S0092-8674(04)00298-3
Reference
  Authors
Yamagata K, Daitoku H, Takahashi Y, Namiki K, Hisatake K, Kako K, Mukai H, Kasuya Y, Fukamizu A
  Title
Arginine methylation of FOXO transcription factors inhibits their phosphorylation by Akt.
  Journal
Mol Cell 32:221-31 (2008)
DOI:10.1016/j.molcel.2008.09.013
Reference
  Authors
van der Horst A, de Vries-Smits AM, Brenkman AB, van Triest MH, van den Broek N, Colland F, Maurice MM, Burgering BM
  Title
FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP.
  Journal
Nat Cell Biol 8:1064-73 (2006)
DOI:10.1038/ncb1469
Reference
  Authors
Zhang Y, Gan B, Liu D, Paik JH
  Title
FoxO family members in cancer.
  Journal
Cancer Biol Ther 12:253-9 (2011)
DOI:10.4161/cbt.12.4.15954
Reference
  Authors
Van Der Heide LP, Hoekman MF, Smidt MP
  Title
The ins and outs of FoxO shuttling: mechanisms of FoxO translocation and transcriptional regulation.
  Journal
Biochem J 380:297-309 (2004)
DOI:10.1042/BJ20040167
Related
pathway
pvt00010  Glycolysis / Gluconeogenesis
pvt00020  Citrate cycle (TCA cycle)
pvt00190  Oxidative phosphorylation
pvt04010  MAPK signaling pathway
pvt04110  Cell cycle
pvt04120  Ubiquitin mediated proteolysis
pvt04140  Autophagy - animal
pvt04210  Apoptosis
pvt04350  TGF-beta signaling pathway
pvt04910  Insulin signaling pathway
KO pathway
ko04068   
LinkDB

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