KEGG   PATHWAY: cjo04068
Entry
cjo04068                    Pathway                                
Name
FoxO signaling pathway - Coturnix japonica (Japanese quail)
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
cjo04068  FoxO signaling pathway
cjo04068

Other DBs
GO: 0009267
Organism
Coturnix japonica (Japanese quail) [GN:cjo]
Gene
107307103  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
107311051  TGFB2; transforming growth factor beta-2 proprotein [KO:K13376]
107315120  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
107309773  LOW QUALITY PROTEIN: TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
107309296  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
107316805  LOW QUALITY PROTEIN: TGF-beta receptor type-2-like [KO:K04388] [EC:2.7.11.30]
107306999  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
107324374  mothers against decapentaplegic homolog 4-like [KO:K04501]
107318915  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
107325449  STK11; serine/threonine-protein kinase STK11 isoform X1 [KO:K07298] [EC:2.7.11.1]
107305860  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
107317703  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
107317110  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
107321393  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
107308766  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
107317021  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200]
107325757  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
107322736  NLK; serine/threonine-protein kinase NLK isoform X1 [KO:K04468] [EC:2.7.11.24]
107305844  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
107310502  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
107313101  SETD7; histone-lysine N-methyltransferase SETD7 [KO:K11431] [EC:2.1.1.364]
107312938  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
107320924  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
107315730  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
107320832  USP7; ubiquitin carboxyl-terminal hydrolase 7 isoform X1 [KO:K11838] [EC:3.4.19.12]
107306987  solute carrier family 2, facilitated glucose transporter member 4-like [KO:K07191]
107313439  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
107315851  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
107320159  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
107322948  STK4; serine/threonine-protein kinase 4 isoform X1 [KO:K04411]
107316281  IGF1; insulin-like growth factor I [KO:K05459]
107318870  IGF1R; insulin-like growth factor 1 receptor precursor [KO:K05087] [EC:2.7.10.1]
107314531  INS; insulin [KO:K04526]
107325585  INSR; insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
107318049  IRS1; insulin receptor substrate 1 [KO:K16172]
107307936  IRS2; insulin receptor substrate 2 isoform X1 [KO:K07187]
107312783  IRS4; insulin receptor substrate 4 [KO:K07187]
107317945  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
107318114  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
107323497  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
107317608  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
107305909  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
107325533  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
107320588  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
107315625  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
107323740  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
107315619  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
107307290  RAC-beta serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
107315293  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
107311258  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
107311699  SGK1; serine/threonine-protein kinase Sgk1 isoform X1 [KO:K13302] [EC:2.7.11.1]
107322884  SGK2; serine/threonine-protein kinase Sgk2 isoform X1 [KO:K13303] [EC:2.7.11.1]
107310235  serine/threonine-protein kinase Sgk3 [KO:K13304] [EC:2.7.11.1]
107308196  FOXO1; forkhead box protein O1 [KO:K07201]
107311812  FOXO3; forkhead box protein O3 [KO:K09408]
107312483  FOXO4; forkhead box protein O4 [KO:K12358]
107324052  FOXO6; forkhead box protein O6 [KO:K17847]
107311576  GRM1; metabotropic glutamate receptor 1 isoform X1 [KO:K04603]
107318731  HOMER2; homer protein homolog 2 isoform X1 [KO:K15010]
107325357  HOMER3; homer protein homolog 3 isoform X2 [KO:K15010]
107305903  HOMER1; homer protein homolog 1 isoform X1 [KO:K15010]
107325350  semaphorin-4E-like isoform X1 [KO:K15010]
107314132  CSNK1E; casein kinase I isoform X1 [KO:K08960] [EC:2.7.11.1]
107309150  IL6; interleukin-6 isoform X1 [KO:K05405]
107324788  IL10; interleukin-10 [KO:K05443]
107325206  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
107313609  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
107309802  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
107322339  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
107315513  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
107310899  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
107314494  HRAS; GTPase HRas isoform X1 [KO:K02833]
107317023  KRAS; GTPase KRas isoform X1 [KO:K07827]
107324818  NRAS; GTPase NRas [KO:K07828]
107315883  BRAF; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:2.7.11.1]
107319673  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
107318921  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
107325595  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
107321038  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
107308592  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
107308531  mitogen-activated protein kinase 12-like [KO:K04441] [EC:2.7.11.24]
107324607  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
107324616  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
107325763  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
116652396  FOXG1; forkhead box protein G1 [KO:K09385]
107318514  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
107312631  CCNB3; G2/mitotic-specific cyclin-B3 isoform X1 [KO:K21771]
107314428  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
107318017  CCND2; G1/S-specific cyclin-D2 isoform X1 [KO:K10151]
107313238  CCNG2; cyclin-G2 [KO:K10146]
107306707  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
107324690  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
107317865  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
107319080  RBL2; retinoblastoma-like protein 2 [KO:K16332]
107320693  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
107306024  PLK2; serine/threonine-protein kinase PLK2 [KO:K08861] [EC:2.7.11.21]
107317517  PLK3; serine/threonine-protein kinase PLK3 [KO:K08862] [EC:2.7.11.21]
107313205  PLK4; serine/threonine-protein kinase PLK4 isoform X2 [KO:K08863] [EC:2.7.11.21]
107317806  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
107325480  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
107306297  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
107310715  BCL2L11; bcl-2-like protein 11 [KO:K16341]
107318308  TNFSF10; tumor necrosis factor ligand superfamily member 10 isoform X1 [KO:K04721]
107318227  BCL6; B-cell lymphoma 6 protein [KO:K15618]
107316268  BNIP3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464]
107306879  uncharacterized protein LOC107306879 [KO:K15464]
107307380  GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
107319320  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
107319475  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 isoform X1 [KO:K08341]
107314403  CAT; catalase [KO:K03781] [EC:1.11.1.6]
107311513  SOD2; superoxide dismutase [Mn], mitochondrial [KO:K04564] [EC:1.15.1.1]
107308373  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
107307214  phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
107323226  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
107316743  G6PC2; glucose-6-phosphatase 2 isoform X1 [KO:K01084] [EC:3.1.3.9]
107325229  G6PC3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
107325302  G6PC; glucose-6-phosphatase [KO:K01084] [EC:3.1.3.9]
107305872  IL7R; interleukin-7 receptor subunit alpha [KO:K05072]
107325646  KLF2; Krueppel-like factor 2 [KO:K17845]
116652400  S1PR1; sphingosine 1-phosphate receptor 1 [KO:K04288]
107325407  S1PR4; sphingosine 1-phosphate receptor 4 [KO:K04293]
107314674  RAG1; V(D)J recombination-activating protein 1 [KO:K10628] [EC:2.3.2.27]
107314705  RAG2; V(D)J recombination-activating protein 2 [KO:K10988]
107312148  FBXO25; F-box only protein 25 isoform X1 [KO:K10305]
107310537  FBXO32; F-box only protein 32 [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
cjo00010  Glycolysis / Gluconeogenesis
cjo00020  Citrate cycle (TCA cycle)
cjo00190  Oxidative phosphorylation
cjo04010  MAPK signaling pathway
cjo04110  Cell cycle
cjo04120  Ubiquitin mediated proteolysis
cjo04140  Autophagy - animal
cjo04210  Apoptosis
cjo04350  TGF-beta signaling pathway
cjo04910  Insulin signaling pathway
KO pathway
ko04068   
LinkDB

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