KEGG   PATHWAY: egz04068
Entry
egz04068                    Pathway                                
Name
FoxO signaling pathway - Egretta garzetta (little egret)
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
egz04068  FoxO signaling pathway
egz04068

Other DBs
GO: 0009267
Organism
Egretta garzetta (little egret) [GN:egz]
Gene
104133428  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
104133279  TGFB3; transforming growth factor beta-3 [KO:K13377]
104125437  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
104122957  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
104128099  TGF-beta receptor type-2-like [KO:K04388] [EC:2.7.11.30]
104134164  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
104125236  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
104127394  STK11; serine/threonine-protein kinase STK11 [KO:K07298] [EC:2.7.11.1]
104133929  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
104123889  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
104129861  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 isoform X1 [KO:K07199]
104132070  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
104130997  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 [KO:K07200]
104132405  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200]
104121926  NLK; serine/threonine-protein kinase NLK [KO:K04468] [EC:2.7.11.24]
104133851  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
104132910  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
104134673  SETD7; histone-lysine N-methyltransferase SETD7 [KO:K11431] [EC:2.1.1.364]
104134337  EP300; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
104121974  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
104124613  SIRT1; NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
104127642  USP7; ubiquitin carboxyl-terminal hydrolase 7 [KO:K11838] [EC:3.4.19.12]
104129145  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
104128427  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
104133994  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
104124962  STK4; serine/threonine-protein kinase 4 [KO:K04411]
104135582  IGF1; insulin-like growth factor I [KO:K05459]
104122851  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
104124907  insulin [KO:K04526]
104124372  INSR; insulin receptor [KO:K04527] [EC:2.7.10.1]
104127063  IRS1; insulin receptor substrate 1 [KO:K16172]
104133285  IRS4; insulin receptor substrate 4 [KO:K07187]
104133065  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
104135481  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
104129991  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
104135641  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
104124880  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
104126253  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
104131301  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
104125140  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
104135306  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
104125131  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]
104131524  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
104125648  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
104131203  SGK1; LOW QUALITY PROTEIN: serine/threonine-protein kinase Sgk1 [KO:K13302] [EC:2.7.11.1]
104132207  SGK2; serine/threonine-protein kinase Sgk2 [KO:K13303] [EC:2.7.11.1]
104122395  SGK3; serine/threonine-protein kinase Sgk3 [KO:K13304] [EC:2.7.11.1]
104129682  FOXO1; forkhead box protein O1 [KO:K07201]
104131578  FOXO3; forkhead box protein O3 [KO:K09408]
104124287  FOXO4; forkhead box protein O4 [KO:K12358]
104132571  FOXO6; forkhead box protein O6 [KO:K17847]
104133563  GRM1; metabotropic glutamate receptor 1 [KO:K04603]
104129785  HOMER3; homer protein homolog 3 isoform X1 [KO:K15010]
104130799  HOMER2; homer protein homolog 2 [KO:K15010]
104124901  HOMER1; homer protein homolog 1 [KO:K15010]
104129804  LOW QUALITY PROTEIN: semaphorin-4D-like [KO:K15010]
104134320  CSNK1E; casein kinase I isoform epsilon [KO:K08960] [EC:2.7.11.1]
104126108  IL6; interleukin-6 [KO:K05405]
104134372  IL10; interleukin-10 [KO:K05443]
104134824  STAT3; LOW QUALITY PROTEIN: signal transducer and activator of transcription 3 [KO:K04692]
104135535  EGF; pro-epidermal growth factor [KO:K04357]
104131586  EGFR; LOW QUALITY PROTEIN: epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
104125396  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
104135007  SOS2; son of sevenless homolog 2 [KO:K03099]
104127966  SOS1; son of sevenless homolog 1 [KO:K03099]
104123569  HRAS; GTPase HRas [KO:K02833]
104135137  KRAS; GTPase KRas isoform X1 [KO:K07827]
104126779  NRAS; GTPase NRas [KO:K07828]
104135588  BRAF; serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
104124306  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
104133527  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
104124397  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
104127223  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
104125693  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
104125710  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
104125751  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
104125670  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
104127409  FOXG1; forkhead box protein G1 [KO:K09385]
104124904  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
104130767  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
104133018  CCNB3; G2/mitotic-specific cyclin-B3 [KO:K21771]
104124693  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
104124210  CCND2; G1/S-specific cyclin-D2 isoform X1 [KO:K10151]
104128687  CCNG2; cyclin-G2 [KO:K10146]
104131411  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
104124226  cyclin-dependent kinase inhibitor 1-like [KO:K06625]
104124192  cyclin-dependent kinase inhibitor 1-like [KO:K06625]
104124225  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
104125194  RBL2; retinoblastoma-like protein 2 [KO:K16332]
104134547  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
104134686  PLK2; serine/threonine-protein kinase PLK2 [KO:K08861] [EC:2.7.11.21]
104126293  PLK3; serine/threonine-protein kinase PLK3 [KO:K08862] [EC:2.7.11.21]
104135662  PLK4; serine/threonine-protein kinase PLK4 [KO:K08863] [EC:2.7.11.21]
104126926  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
104132069  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
104128140  BCL2L11; bcl-2-like protein 11 [KO:K16341]
104132497  TNFSF10; LOW QUALITY PROTEIN: tumor necrosis factor ligand superfamily member 10 [KO:K04721]
104123372  BCL6; B-cell lymphoma 6 protein [KO:K15618]
104124970  BNIP3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464]
104126292  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
104124202  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
104124683  CAT; catalase [KO:K03781] [EC:1.11.1.6]
104124809  SOD2; superoxide dismutase [Mn], mitochondrial [KO:K04564] [EC:1.15.1.1]
104130058  ATM; LOW QUALITY PROTEIN: serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
104132180  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
104134721  G6PC; glucose-6-phosphatase isoform X1 [KO:K01084] [EC:3.1.3.9]
104128036  G6PC2; glucose-6-phosphatase 2 isoform X1 [KO:K01084] [EC:3.1.3.9]
104133924  IL7R; interleukin-7 receptor subunit alpha [KO:K05072]
104124415  KLF2; Krueppel-like factor 2 [KO:K17845]
104134037  S1PR1; LOW QUALITY PROTEIN: sphingosine 1-phosphate receptor 1 [KO:K04288]
104124378  S1PR4; sphingosine 1-phosphate receptor 4 [KO:K04293]
104134047  RAG1; V(D)J recombination-activating protein 1 [KO:K10628] [EC:2.3.2.27]
104134048  RAG2; V(D)J recombination-activating protein 2 [KO:K10988]
104123679  FBXO32; F-box only protein 32 [KO:K10305]
104122170  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
egz00010  Glycolysis / Gluconeogenesis
egz00020  Citrate cycle (TCA cycle)
egz00190  Oxidative phosphorylation
egz04010  MAPK signaling pathway
egz04110  Cell cycle
egz04120  Ubiquitin mediated proteolysis
egz04140  Autophagy - animal
egz04210  Apoptosis
egz04350  TGF-beta signaling pathway
egz04910  Insulin signaling pathway
KO pathway
ko04068   
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