KEGG   PATHWAY: canu04068
Entry
canu04068                   Pathway                                
Name
FoxO signaling pathway - Magallana angulata (Portugese oyster)
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
canu04068  FoxO signaling pathway
canu04068

Other DBs
GO: 0009267
Organism
Magallana angulata (Portugese oyster) [GN:canu]
Gene
128155139  TGF-beta receptor type-1-like [KO:K04674] [EC:2.7.11.30]
128173425  mothers against decapentaplegic homolog 4-like isoform X1 [KO:K04501]
128171544  mothers against decapentaplegic homolog 3-like isoform X1 [KO:K23605]
128173082  mothers against decapentaplegic homolog 3-like [KO:K23605]
128173169  mothers against decapentaplegic homolog 2-like [KO:K23605]
128166179  serine/threonine-protein kinase STK11-like [KO:K07298] [EC:2.7.11.1]
128165229  5'-AMP-activated protein kinase catalytic subunit alpha-2-like isoform X1 [KO:K07198] [EC:2.7.11.31]
128175514  5'-AMP-activated protein kinase subunit beta-1-like isoform X1 [KO:K07199]
128163149  5'-AMP-activated protein kinase subunit gamma-2-like isoform X1 [KO:K07200]
128190364  serine/threonine-protein kinase NLK-like isoform X1 [KO:K04468] [EC:2.7.11.24]
128165279  S-phase kinase-associated protein 2-like [KO:K03875]
128192100  CREB-binding protein-like isoform X1 [KO:K04498] [EC:2.3.1.48]
128167321  NAD-dependent protein deacetylase sirtuin-1-like [KO:K11411] [EC:2.3.1.286]
128168293  ubiquitin carboxyl-terminal hydrolase 7-like isoform X1 [KO:K11838] [EC:3.4.19.12]
128164696  stress-activated protein kinase JNK-like isoform X1 [KO:K04440] [EC:2.7.11.24]
128184248  con-Ins Im2-like [KO:K04526]
128177663  insulin-like peptide receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
128188289  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform-like [KO:K00922] [EC:2.7.1.153]
128188793  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like isoform X1 [KO:K00922] [EC:2.7.1.153]
128165077  phosphatidylinositol 3-kinase regulatory subunit alpha-like isoform X1 [KO:K02649]
128166562  3-phosphoinositide-dependent protein kinase 1-like [KO:K06276] [EC:2.7.11.1]
128165598  inhibitor of nuclear factor kappa-B kinase subunit alpha-like isoform X1 [KO:K04467] [EC:2.7.11.10]
128165600  inhibitor of nuclear factor kappa-B kinase subunit alpha-like [KO:K04467] [EC:2.7.11.10]
128165226  phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN-like [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
128178921  RAC-alpha serine/threonine-protein kinase-like isoform X1 [KO:K04456] [EC:2.7.11.1]
128164452  serine/threonine-protein kinase Sgk1-like isoform X1 [KO:K13304] [EC:2.7.11.1]
128183345  forkhead box protein O-like [KO:K09408]
128176453  homer protein homolog 2-like isoform X1 [KO:K15010]
128157355  epidermal growth factor receptor-like isoform X1 [KO:K04361] [EC:2.7.10.1]
128166290  growth factor receptor-bound protein 2-like isoform X1 [KO:K04364]
128175075  son of sevenless homolog 2-like [KO:K03099]
128188515  GTPase HRas [KO:K07827]
128159074  serine/threonine-protein kinase B-raf-like isoform X1 [KO:K04365] [EC:2.7.11.1]
128175496  dual specificity mitogen-activated protein kinase kinase 1-like isoform X1 [KO:K04368] [EC:2.7.12.2]
128188086  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
128158243  mitogen-activated protein kinase 14-like isoform X1 [KO:K04441] [EC:2.7.11.24]
128190235  cyclin-dependent kinase 2-like [KO:K02206] [EC:2.7.11.22]
128166193  protein arginine N-methyltransferase 1-like [KO:K11434] [EC:2.1.1.319]
128176611  forkhead box protein G1-like [KO:K09385]
128186583  G2/mitotic-specific cyclin-B-like isoform X1 [KO:K05868]
128177950  G2/mitotic-specific cyclin-B-like [KO:K21770]
128158020  G2/mitotic-specific cyclin-B-like isoform X1 [KO:K21770]
128181246  G2/mitotic-specific cyclin-B3-like [KO:K21771]
128184092  G1/S-specific cyclin-D2-like [KO:K10151]
128178483  serine/threonine-protein kinase PLK1-like [KO:K06631] [EC:2.7.11.21]
128165708  serine/threonine-protein kinase PLK1-like [KO:K08861] [EC:2.7.11.21]
128155706  serine/threonine-protein kinase PLK4-like isoform X1 [KO:K08863] [EC:2.7.11.21]
128164502  growth arrest and DNA damage-inducible protein GADD45 gamma-like [KO:K04402]
128165744  uncharacterized protein LOC128165744 isoform X1 [KO:K04402]
128165745  uncharacterized protein LOC128165745 [KO:K04402]
128168165  growth arrest and DNA damage-inducible protein GADD45 alpha-like [KO:K04402]
128168383  growth arrest and DNA damage-inducible protein GADD45 gamma-like [KO:K04402]
128181208  uncharacterized protein LOC128181208 [KO:K04389]
128180037  tumor necrosis factor ligand superfamily member 10-like [KO:K04721]
128181302  tumor necrosis factor ligand superfamily member 11-like [KO:K04721]
128179934  BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like [KO:K15464]
128167652  ubiquitin-like protein ATG12 [KO:K08336]
128189396  gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
128188633  gamma-aminobutyric acid receptor-associated protein [KO:K08341]
128184253  catalase-like isoform X1 [KO:K03781] [EC:1.11.1.6]
128184382  catalase-like [KO:K03781] [EC:1.11.1.6]
128183921  superoxide dismutase [Mn], mitochondrial-like [KO:K04564] [EC:1.15.1.1]
128187121  serine-protein kinase ATM-like [KO:K04728] [EC:2.7.11.1]
128189255  phosphoenolpyruvate carboxykinase, cytosolic [GTP]-like isoform X1 [KO:K01596] [EC:4.1.1.32]
128188722  phosphoenolpyruvate carboxykinase [GTP]-like [KO:K01596] [EC:4.1.1.32]
128184552  glucose-6-phosphatase 2-like [KO:K01084] [EC:3.1.3.9]
128165486  Krueppel-like factor 3 [KO:K17845]
128167441  F-box only protein 25-like [KO:K10305]
128159569  F-box only protein 25-like [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
canu00010  Glycolysis / Gluconeogenesis
canu00020  Citrate cycle (TCA cycle)
canu00190  Oxidative phosphorylation
canu04120  Ubiquitin mediated proteolysis
canu04140  Autophagy - animal
canu04350  TGF-beta signaling pathway
KO pathway
ko04068   
LinkDB

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