KEGG   PATHWAY: achl04068
Entry
achl04068                   Pathway                                
Name
FoxO signaling pathway - Acanthisitta chloris (rifleman)
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
achl04068  FoxO signaling pathway
achl04068

Other DBs
GO: 0009267
Organism
Acanthisitta chloris (rifleman) [GN:achl]
Gene
103811139  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
103807798  TGFB3; transforming growth factor beta-3 [KO:K13377]
103800140  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
103805135  TGF-beta receptor type-2-like [KO:K04388] [EC:2.7.11.30]
103811946  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
103809398  LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 4-like [KO:K04501]
103808962  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
103799764  STK11; serine/threonine-protein kinase STK11 [KO:K07298] [EC:2.7.11.1]
103807193  PRKAA2; LOW QUALITY PROTEIN: 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
103809143  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
103811089  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
103809016  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 isoform X1 [KO:K07199]
103804611  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200]
103808107  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 [KO:K07200]
103807978  NLK; serine/threonine-protein kinase NLK [KO:K04468] [EC:2.7.11.24]
103808307  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
103799310  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
103811991  SETD7; histone-lysine N-methyltransferase SETD7 [KO:K11431] [EC:2.1.1.364]
103811286  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
103811709  CREBBP; LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:2.3.1.48]
103811067  SIRT1; LOW QUALITY PROTEIN: NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
103806734  USP7; ubiquitin carboxyl-terminal hydrolase 7 [KO:K11838] [EC:3.4.19.12]
103811480  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
103812215  mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
103806889  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
103804870  STK4; serine/threonine-protein kinase 4 [KO:K04411]
103804378  IGF1; insulin-like growth factor I [KO:K05459]
103798238  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
103802297  INS; insulin [KO:K04526]
103800983  LOW QUALITY PROTEIN: insulin receptor-like [KO:K04527] [EC:2.7.10.1]
103802148  LOW QUALITY PROTEIN: insulin receptor substrate 2-B-like [KO:K07187]
103797203  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103801633  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
103801693  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
103800635  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
103807634  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
103807943  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
103798629  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
103805825  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
103798520  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
103811716  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]
103801923  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103808494  SGK1; serine/threonine-protein kinase Sgk1 isoform X1 [KO:K13302] [EC:2.7.11.1]
103812084  SGK2; serine/threonine-protein kinase Sgk2 [KO:K13303] [EC:2.7.11.1]
103807786  serine/threonine-protein kinase Sgk3 [KO:K13304] [EC:2.7.11.1]
103804506  FOXO1; LOW QUALITY PROTEIN: forkhead box protein O1 [KO:K07201]
103805273  FOXO3; forkhead box protein O3 [KO:K09408]
103797557  FOXO4; forkhead box protein O4 [KO:K12358]
103800092  metabotropic glutamate receptor 1-like [KO:K04603]
103804335  homer protein homolog 1 [KO:K15010]
103805371  HOMER3; homer protein homolog 3 [KO:K15010]
103811292  HOMER2; homer protein homolog 2 [KO:K15010]
103799990  CSNK1E; casein kinase I isoform epsilon [KO:K08960] [EC:2.7.11.1]
103797180  IL6; interleukin-6 [KO:K05405]
103804662  IL10; interleukin-10 [KO:K05443]
103797727  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
103797310  pro-epidermal growth factor-like [KO:K04357]
103800957  pro-epidermal growth factor-like [KO:K04357]
103810188  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
103810694  SOS2; son of sevenless homolog 2 [KO:K03099]
103808944  SOS1; son of sevenless homolog 1 [KO:K03099]
103801883  HRAS; GTPase HRas [KO:K02833]
103804109  KRAS; GTPase KRas isoform X1 [KO:K07827]
103811226  GTPase NRas [KO:K07828]
103807473  BRAF; serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
103811193  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
103809856  dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103802868  LOW QUALITY PROTEIN: mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
103797444  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
103797445  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
103807808  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
103808070  mitogen-activated protein kinase 11-like [KO:K04441] [EC:2.7.11.24]
103797968  FOXG1; forkhead box protein G1 [KO:K09385]
103808424  LOW QUALITY PROTEIN: G2/mitotic-specific cyclin-B1-like [KO:K05868]
103801751  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
103810712  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
103801578  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
103797654  CCNG2; cyclin-G2 [KO:K10146]
103806291  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
103802142  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
103807663  RBL2; retinoblastoma-like protein 2 [KO:K16332]
103807661  PLK1; LOW QUALITY PROTEIN: serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
103809938  PLK2; serine/threonine-protein kinase PLK2 [KO:K08861] [EC:2.7.11.21]
103800484  PLK3; LOW QUALITY PROTEIN: serine/threonine-protein kinase PLK3 [KO:K08862] [EC:2.7.11.21]
103811318  PLK4; serine/threonine-protein kinase PLK4 [KO:K08863] [EC:2.7.11.21]
103806780  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
103803923  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
103806153  tumor necrosis factor ligand superfamily member 10-like [KO:K04721]
103801655  BCL6; B-cell lymphoma 6 protein [KO:K15618]
103798432  BNIP3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464]
103806626  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
103803377  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
103810953  CAT; catalase [KO:K03781] [EC:1.11.1.6]
103799934  SOD2; superoxide dismutase [Mn], mitochondrial [KO:K04564] [EC:1.15.1.1]
103803496  ATM; LOW QUALITY PROTEIN: serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
103799799  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] isoform X1 [KO:K01596] [EC:4.1.1.32]
103803588  G6PC2; glucose-6-phosphatase 2 isoform X1 [KO:K01084] [EC:3.1.3.9]
103812038  G6PC3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
103808798  G6PC; glucose-6-phosphatase [KO:K01084] [EC:3.1.3.9]
103804055  IL7R; interleukin-7 receptor subunit alpha [KO:K05072]
103806811  LOW QUALITY PROTEIN: Krueppel-like factor 2 [KO:K17845]
103799288  LOW QUALITY PROTEIN: sphingosine 1-phosphate receptor 1-like [KO:K04288]
103800860  S1PR4; LOW QUALITY PROTEIN: sphingosine 1-phosphate receptor 4 [KO:K04293]
103806229  RAG1; V(D)J recombination-activating protein 1 [KO:K10628] [EC:2.3.2.27]
103806230  RAG2; V(D)J recombination-activating protein 2 [KO:K10988]
103809581  FBXO25; F-box only protein 25 isoform X1 [KO:K10305]
103801957  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
achl00010  Glycolysis / Gluconeogenesis
achl00020  Citrate cycle (TCA cycle)
achl00190  Oxidative phosphorylation
achl04010  MAPK signaling pathway
achl04110  Cell cycle
achl04120  Ubiquitin mediated proteolysis
achl04140  Autophagy - animal
achl04210  Apoptosis
achl04350  TGF-beta signaling pathway
achl04910  Insulin signaling pathway
KO pathway
ko04068   
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