KEGG   PATHWAY: mcoc04068
Entry
mcoc04068                   Pathway                                
Name
FoxO signaling pathway - Mastomys coucha (southern multimammate mouse)
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
mcoc04068  FoxO signaling pathway
mcoc04068

Other DBs
GO: 0009267
Organism
Mastomys coucha (southern multimammate mouse) [GN:mcoc]
Gene
116067982  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
116068264  Prkab1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
116068447  Tgfb2; transforming growth factor beta-2 proprotein [KO:K13376]
116068604  [KO:K17445]
116068825  Insr; insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
116068902  Irs2; insulin receptor substrate 2 [KO:K07187]
116068952  Fbxo25; F-box only protein 25 isoform X1 [KO:K10305]
116069014  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
116069457  Homer3; homer protein homolog 3 [KO:K15010]
116069491  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
116069549  Klf2; Krueppel-like factor 2 [KO:K17845]
116069845  Rbl2; retinoblastoma-like protein 2 [KO:K16332]
116070135  Il10; interleukin-10 [KO:K05443]
116070214  Gabarapl2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
116070785  Faslg; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
116071392  Egfr; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
116073048  Ccnb2; G2/mitotic-specific cyclin-B2 [KO:K21770]
116073193  Smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
116073222  Atm; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
116073579  Tgfbr2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
116073648  Mapk6; mitogen-activated protein kinase 6 [KO:K04371] [EC:2.7.11.24]
116073764  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
116073820  Araf; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
116073909  Cdkn2d; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
116073929  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116075101  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
116075178  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
116075265  Sirt1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
116075286  Foxo3; forkhead box protein O3 [KO:K09408]
116075516  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
116075683  Agap2; arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 isoform X1 [KO:K17848]
116075868  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
116075903  [KO:K08960] [EC:2.7.11.1]
116075923  Mdm2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
116076013  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
116076083  S1pr4; sphingosine 1-phosphate receptor 4 [KO:K04293]
116076163  Cdk2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
116076368  Ep300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
116076407  Igf1; insulin-like growth factor I isoform X1 [KO:K05459]
116076582  Stk11; serine/threonine-protein kinase STK11 isoform X1 [KO:K07298] [EC:2.7.11.1]
116076719  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
116076765  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
116076801  Stat3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
116076828  G6pc3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
116077104  Gabarap; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
116077179  Nlk; serine/threonine-protein kinase NLK [KO:K04468] [EC:2.7.11.24]
116077765  Mapk11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
116077791  Mapk12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
116077838  G6pc; glucose-6-phosphatase [KO:K01084] [EC:3.1.3.9]
116078189  Pdpk1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
116078242  Sod2; superoxide dismutase [Mn], mitochondrial [KO:K04564] [EC:1.15.1.1]
116079077  Slc2a4; solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191]
116079191  Prkag1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
116079779  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
116080097  Tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
116080098  Foxg1; forkhead box protein G1 [KO:K09385]
116080813  Sos1; son of sevenless homolog 1 [KO:K03099]
116080934  Sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
116081743  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
116082037  Fbxo32; F-box only protein 32 [KO:K10305]
116083203  Prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
116083490  Il7r; interleukin-7 receptor subunit alpha [KO:K05072]
116083574  Plk2; serine/threonine-protein kinase PLK2 [KO:K08861] [EC:2.7.11.21]
116083582  Ccnb1; G2/mitotic-specific cyclin-B1 [KO:K05868]
116083721  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
116083766  Homer1; homer protein homolog 1 [KO:K15010]
116083772  Skp2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
116084175  Crebbp; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
116084755  Pck2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
116084844  Usp7; ubiquitin carboxyl-terminal hydrolase 7 isoform X1 [KO:K11838] [EC:3.4.19.12]
116085336  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
116085641  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
116085757  Bcl6; B-cell lymphoma 6 protein [KO:K15618]
116087137  Atg12; ubiquitin-like protein ATG12 isoform X1 [KO:K08336]
116087162  Foxo4; forkhead box protein O4 [KO:K12358]
116087335  Smad4; mothers against decapentaplegic homolog 4 [KO:K04501]
116088156  [KO:K13304] [EC:2.7.11.1]
116088583  Prkag3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200]
116088647  Irs1; insulin receptor substrate 1 [KO:K16172]
116089083  Irs4; LOW QUALITY PROTEIN: insulin receptor substrate 4 [KO:K17446]
116090548  Rag2; V(D)J recombination-activating protein 2 [KO:K10988]
116090569  Cat; catalase [KO:K03781] [EC:1.11.1.6]
116090896  Bcl2l11; bcl-2-like protein 11 isoform X1 [KO:K16341]
116091335  Sgk2; serine/threonine-protein kinase Sgk2 [KO:K13303] [EC:2.7.11.1]
116091355  Stk4; serine/threonine-protein kinase 4 isoform X1 [KO:K04411]
116091552  Ccnb3; G2/mitotic-specific cyclin-B3 [KO:K21771]
116092006  G6pc2; LOW QUALITY PROTEIN: glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
116092256  Rag1; V(D)J recombination-activating protein 1 [KO:K10628] [EC:2.3.2.27]
116092572  Pck1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
116093481  Prkab2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
116093530  Nras; GTPase NRas [KO:K07828]
116093668  S1pr1; sphingosine 1-phosphate receptor 1 [KO:K04288]
116093773  Egf; pro-epidermal growth factor [KO:K04357]
116094448  Setd7; histone-lysine N-methyltransferase SETD7 [KO:K11431] [EC:2.1.1.364]
116094452  Foxo1; forkhead box protein O1 [KO:K07201]
116095017  Tnfsf10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
116095058  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116095130  Plk4; serine/threonine-protein kinase PLK4 isoform X1 [KO:K08863] [EC:2.7.11.21]
116095983  Tgfbr1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
116096225  Cdkn2b; cyclin-dependent kinase 4 inhibitor B isoform X1 [KO:K04685]
116096329  Prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
116096465  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
116096490  Plk3; serine/threonine-protein kinase PLK3 [KO:K08862] [EC:2.7.11.21]
116096545  Foxo6; forkhead box protein O6 [KO:K17847]
116097037  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116097436  Il6; interleukin-6 [KO:K05405]
116097568  Prkag2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
116097763  Grm1; metabotropic glutamate receptor 1 isoform X1 [KO:K04603]
116097831  Sgk1; serine/threonine-protein kinase Sgk1 isoform X1 [KO:K13302] [EC:2.7.11.1]
116098774  Braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
116099018  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
116099433  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
116099455  Depp1; protein DEPP1 [KO:K27679]
116099629  Ccnd2; G1/S-specific cyclin-D2 [KO:K10151]
116099677  Gabarapl1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
116099702  Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
116099791  Kras; GTPase KRas isoform X1 [KO:K07827]
116101220  Prmt1; protein arginine N-methyltransferase 1 [KO:K11434] [EC:2.1.1.319]
116101481  [KO:K04526]
116101857  Tgfb1; transforming growth factor beta-1 proprotein [KO:K13375]
116101889  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
116102373  Igf1r; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
116102489  Homer2; homer protein homolog 2 isoform X1 [KO:K15010]
116102914  Plk1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
116102969  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
116103150  Bnip3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464]
116103285  Ccnd1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
116103746  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]
116103881  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
116104026  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
116104593  Ccng2; cyclin-G2 [KO:K10146]
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
mcoc00010  Glycolysis / Gluconeogenesis
mcoc00020  Citrate cycle (TCA cycle)
mcoc00190  Oxidative phosphorylation
mcoc04010  MAPK signaling pathway
mcoc04110  Cell cycle
mcoc04120  Ubiquitin mediated proteolysis
mcoc04140  Autophagy - animal
mcoc04151  PI3K-Akt signaling pathway
mcoc04210  Apoptosis
mcoc04350  TGF-beta signaling pathway
mcoc04630  JAK-STAT signaling pathway
mcoc04910  Insulin signaling pathway
KO pathway
ko04068   

DBGET integrated database retrieval system