KEGG   PATHWAY: pyu04068
Entry
pyu04068                    Pathway                                
Name
FoxO signaling pathway - Puma yagouaroundi (jaguarundi)
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
pyu04068  FoxO signaling pathway
pyu04068

Other DBs
GO: 0009267
Organism
Puma yagouaroundi (jaguarundi) [GN:pyu]
Gene
121009809  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 isoform X1 [KO:K08341]
121010247  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
121010516  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
121010556  ATG12; ubiquitin-like protein ATG12 isoform X1 [KO:K08336]
121011002  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
121011036  HOMER3; homer protein homolog 3 [KO:K15010]
121011444  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
121012141  STK4; serine/threonine-protein kinase 4 [KO:K04411]
121012171  SGK2; serine/threonine-protein kinase Sgk2 isoform X1 [KO:K13303] [EC:2.7.11.1]
121012848  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
121012888  FOXO1; forkhead box protein O1 [KO:K07201]
121013230  SOD2; superoxide dismutase [Mn], mitochondrial [KO:K04564] [EC:1.15.1.1]
121013347  GRM1; metabotropic glutamate receptor 1 isoform X1 [KO:K04603]
121013433  SGK1; serine/threonine-protein kinase Sgk1 isoform X1 [KO:K13302] [EC:2.7.11.1]
121013741  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
121013826  INSR; insulin receptor [KO:K04527] [EC:2.7.10.1]
121013983  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
121013990  HOMER1; homer protein homolog 1 isoform X1 [KO:K15010]
121014485  IRS1; insulin receptor substrate 1 [KO:K16172]
121014916  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
121014969  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
121015025  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
121015111  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
121015634  PLK2; serine/threonine-protein kinase PLK2 [KO:K08861] [EC:2.7.11.21]
121016014  SLC2A4; solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191]
121016026  [KO:K08341]
121016570  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]
121017018  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
121017182  NLK; serine/threonine-protein kinase NLK isoform X1 [KO:K04468] [EC:2.7.11.24]
121017578  FOXO6; forkhead box protein O6 [KO:K17847]
121017634  [KO:K17445]
121017912  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
121018482  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
121018790  [KO:K11434] [EC:2.1.1.319]
121019375  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
121019544  USP7; ubiquitin carboxyl-terminal hydrolase 7 isoform X1 [KO:K11838] [EC:3.4.19.12]
121019602  [KO:K04498] [EC:2.3.1.48]
121019662  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
121019899  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
121020585  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
121020862  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
121021348  S1PR4; sphingosine 1-phosphate receptor 4 [KO:K04293]
121021432  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
121021465  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
121021482  STK11; serine/threonine-protein kinase STK11 isoform X1 [KO:K07298] [EC:2.7.11.1]
121021821  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
121021950  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
121022226  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
121022407  IL10; interleukin-10 [KO:K05443]
121022826  HRAS; GTPase HRas isoform X1 [KO:K02833]
121022970  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
121023018  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
121023852  CCND1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
121023965  INS; insulin [KO:K04526]
121024217  IRS2; insulin receptor substrate 2 [KO:K07187]
121024845  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
121025237  FOXO4; forkhead box protein O4 [KO:K12358]
121025718  IRS4; LOW QUALITY PROTEIN: insulin receptor substrate 4 [KO:K17446]
121025949  CCNB3; G2/mitotic-specific cyclin-B3 isoform X1 [KO:K21771]
121026094  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
121027020  PLK3; serine/threonine-protein kinase PLK3 [KO:K08862] [EC:2.7.11.21]
121027050  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
121027198  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
121027286  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
121027572  S1PR1; sphingosine 1-phosphate receptor 1 [KO:K04288]
121027738  NRAS; GTPase NRas [KO:K07828]
121028241  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
121028638  IL6; interleukin-6 isoform X1 [KO:K05405]
121029354  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
121029356  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
121029363  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
121029498  SETD7; histone-lysine N-methyltransferase SETD7 isoform X1 [KO:K11431] [EC:2.1.1.364]
121029870  FOXO3; forkhead box protein O3 [KO:K09408]
121029875  PLK4; serine/threonine-protein kinase PLK4 [KO:K08863] [EC:2.7.11.21]
121030255  G6PC2; glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
121031012  EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
121031080  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200]
121031535  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1 [KO:K01596] [EC:4.1.1.32]
121031599  FOXG1; forkhead box protein G1 [KO:K09385]
121031737  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
121032078  TGFB3; transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
121032358  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
121032920  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
121033019  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
121033562  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
121033733  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
121033870  CCNG2; cyclin-G2 isoform X1 [KO:K10146]
121033998  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
121034018  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
121034137  BCL6; B-cell lymphoma 6 protein isoform X1 [KO:K15618]
121034524  [KO:K04685]
121034732  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
121035348  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
121036697  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
121036923  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
121036953  DEPP1; protein DEPP1 [KO:K27679]
121037105  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
121037403  BNIP3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464]
121038165  SGK3; serine/threonine-protein kinase Sgk3 isoform X1 [KO:K13304] [EC:2.7.11.1]
121038634  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
121038809  KRAS; GTPase KRas isoform X1 [KO:K07827]
121038909  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
121038952  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
121039579  FBXO25; F-box only protein 25 isoform X1 [KO:K10305]
121040120  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
121040286  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
121040352  CSNK1E; casein kinase I isoform X1 [KO:K08960] [EC:2.7.11.1]
121040524  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
121040772  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
121040856  AGAP2; arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 isoform X1 [KO:K17848]
121040954  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
121041241  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
121041777  CCNB2; G2/mitotic-specific cyclin-B2 isoform X1 [KO:K21770]
121041863  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
121041878  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
121042326  HOMER2; homer protein homolog 2 isoform X1 [KO:K15010]
121042474  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
121042942  FBXO32; F-box only protein 32 [KO:K10305]
121043454  IL7R; interleukin-7 receptor subunit alpha [KO:K05072]
121043524  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
121043531  RAG2; V(D)J recombination-activating protein 2 [KO:K10988]
121043533  RAG1; V(D)J recombination-activating protein 1 [KO:K10628] [EC:2.3.2.27]
121043560  CAT; catalase [KO:K03781] [EC:1.11.1.6]
121043998  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
121044367  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
121044434  BCL2L11; bcl-2-like protein 11 isoform X1 [KO:K16341]
121045024  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
121045051  G6PC1; glucose-6-phosphatase isoform X1 [KO:K01084] [EC:3.1.3.9]
121045083  G6PC3; glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
121045294  RBL2; retinoblastoma-like protein 2 [KO:K16332]
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
pyu00010  Glycolysis / Gluconeogenesis
pyu00020  Citrate cycle (TCA cycle)
pyu00190  Oxidative phosphorylation
pyu04010  MAPK signaling pathway
pyu04110  Cell cycle
pyu04120  Ubiquitin mediated proteolysis
pyu04140  Autophagy - animal
pyu04151  PI3K-Akt signaling pathway
pyu04210  Apoptosis
pyu04350  TGF-beta signaling pathway
pyu04630  JAK-STAT signaling pathway
pyu04910  Insulin signaling pathway
KO pathway
ko04068   

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