Embryonic stem cell pluripotency pathways (Homo sapiens)

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4PSelf-renewalInhibits self-renewal (promotes differentiation)Non-canonical pathwayRas/ERK pathwayPKCLIF signalingGi signalingG12 signalingGPCR-arrestin signalsSelf-renewal-p-p DephosphorylationWnt signalingBMP signalingSelf-renewalBindingFrizzled ligandsNucleusJNKSelf-renewalDegradation of beta-cateninPhophorylatedR-Smad / Co-Smad complexPDEPI3 Kinase / Akt signalingPromotes self-renewal (inhibits differentiation)RAF1FGF5WNT9BACVR2BFGF6ELK1FZD1PIP3MAP2K5DVL3PDGFRAGRB2FZD8FGF17FGFR3NOGFGFR4IL6STBRAFFGF8PDGFAMAP2K3LRP5SMAD5MAPK7WNT7ASMAD5STAT3APCWNT2MTORFGF11ERASFZD7PIP2LIFRSMAD4MAPK4GTPCTNNB1DVL1MDM2SMAD9FGFR2FGF20HRASSOS1LIFAKT3FGF14STAT3GSK3BSMAD5WNT10ASMAD1FOSWNT16IKKWNT11FZD6PIP2FGF3FGF22FGF4SELENOPEGFRWNT10BWNT6HNF1AFZD2ACVR1FZD9LRP6WNT2BDorsomorphinACTR2BMPR1BMAPK1AKT2SMAD1WNT5AFGF16MAP2K6FGF10FGF13MAP2K1PTENSMAD1FGF23FZD4MAP2K2FGF19FGF2FGF1BMP4PDGFBCa2+FGF7WNT3ASMAD9FZD3FGF21DVL2PIK3CDJUNFGFR1BMPR2SMAD9MAPK12GDPWNT4WNT1FGF9ARAFGAB1BMPR1AJAK1FGF12SMAD7CTNNB1WNT5BSTAT3PTPN11EGFPIK3R2AKT1FZD5MycSMAD6PDGFRBSTAT3WNT7BAXIN1FGF18WNT3CTNNB1MAPK6P1, 3PPPPPPSMAD4PP2PPPPSMAD1SMAD5SMAD9SMAD4STAT3STAT3PPTPN11JAK1HRASLegend


Description

The cytokine LIF and its downstream effector STAT3 are essential for maintenance of pluripotency in mouse ES cells. The requirement for the transcription factor Oct3/4 for ES cell pluripotency is also well-documented. However, LIF is not involved in self-renewal of human ES cells, suggesting that other pathways must play an important role in this process. The importance of other signal transduction pathways, including BMP and Wnt signalings, as well as novel transcription factors such as Nanog, is now being recognized.

Pathway source: Intracellular Signaling Pathways Regulating Pluripotency of Embryonic Stem Cells, Okita et al, Current Stem Cell Research and Therapy, 2006, 1, 103-111.

Proteins on this pathway have targeted assays available via the CPTAC Assay Portal

Comments

HomologyMapper 
This pathway was inferred from Mus musculus pathway "ESC Pluripotency Pathways", WP339 revision 9831, with a 97.0% conversion rate.

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Ontology Terms

 

Bibliography

  1. Hao J, Daleo MA, Murphy CK, Yu PB, Ho JN, Hu J, Peterson RT, Hatzopoulos AK, Hong CC; ''Dorsomorphin, a selective small molecule inhibitor of BMP signaling, promotes cardiomyogenesis in embryonic stem cells.''; PLoS ONE, 2008 PubMed Europe PMC Scholia
  2. Yuasa S, Itabashi Y, Koshimizu U, Tanaka T, Sugimura K, Kinoshita M, Hattori F, Fukami S, Shimazaki T, Ogawa S, Okano H, Fukuda K; ''Transient inhibition of BMP signaling by Noggin induces cardiomyocyte differentiation of mouse embryonic stem cells.''; Nat Biotechnol, 2005 PubMed Europe PMC Scholia
  3. Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Goodyear LJ, Moller DE; ''Role of AMP-activated protein kinase in mechanism of metformin action.''; J Clin Invest, 2001 PubMed Europe PMC Scholia
  4. Okita K, Yamanaka S; ''Intracellular signaling pathways regulating pluripotency of embryonic stem cells.''; Curr Stem Cell Res Ther, 2006 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
134286view05:34, 20 July 2024EgonwRemoved template comments
131794view16:42, 3 June 2024Khanspersupdated unannotated node
130964view12:03, 31 May 2024EweitzRefine legend
130963view12:00, 31 May 2024EweitzStandardize case
130962view11:58, 31 May 2024EweitzEconomize layout
127829view11:50, 22 December 2023EweitzOntology Term : 'PW:0000102' removed !
117717view12:31, 22 May 2021EweitzModified title
106768view13:24, 17 September 2019MaintBotHMDB identifier normalization
106396view21:29, 28 August 2019KhanspersModified description
105576view06:31, 9 August 2019KhanspersModified description
102153view19:06, 4 December 2018Khanspersupdated Z83313.1 to FGF13
94310view11:58, 1 September 2017Marvin M2Changed arrow and connected unconnected line
94210view21:24, 25 August 2017DeSlAdded ID for PIP2. Cannot find unconencted line :(
91005view13:21, 20 December 2016ElisaFixed unconnected lines
90947view03:59, 19 December 2016Khanspersupdated description
90750view23:40, 13 December 2016Khanspersupdated source pathway information
90749view23:39, 13 December 2016KhanspersOntology Term : 'embryonic stem cell' added !
90748view23:39, 13 December 2016KhanspersOntology Term : 'the extracellular signal-regulated Raf/Mek/Erk signaling pathway' added !
90747view23:38, 13 December 2016KhanspersNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ACTR2GeneProductENSG00000138071 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:66713
ACVR1GeneProductENSG00000115170 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:11477
ACVR2BGeneProduct93 (Entrez Gene)
AKT1GeneProductENSG00000142208 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:11651
AKT2GeneProductENSG00000105221 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:11652
AKT3GeneProductENSG00000117020 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:23797
APCGeneProductENSG00000134982 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:11789
ARAFGeneProductENSG00000078061 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:11836
AXIN1GeneProductENSG00000103126 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:12005
BMP4GeneProductENSG00000125378 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:12159
BMPR1AGeneProductENSG00000107779 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:12166
BMPR1BGeneProductENSG00000138696 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:12167
BMPR2GeneProductENSG00000204217 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:12168
BRAFGeneProductENSG00000157764 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:109880
CTNNB1GeneProductENSG00000168036 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:12387
Ca2+MetaboliteHMDB0000464 (HMDB)
DVL1GeneProductENSG00000107404 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:13542
DVL2GeneProductENSG00000004975 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:13543
DVL3GeneProductENSG00000161202 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:13544
DorsomorphinMetaboliteCHEBI:78510 (ChEBI) Also known as Compound C
EGFGeneProductENSG00000138798 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:13645
EGFRGeneProductENSG00000146648 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:13649
ELK1GeneProductENSG00000126767 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:13712
ERASGeneProductENSG00000187682 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:353283
FGF10GeneProductENSG00000070193 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14165
FGF11GeneProductENSG00000161958 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14166
FGF12GeneProductENSG00000114279 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14167
FGF13GeneProductENSG00000129682 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14168
FGF14GeneProductENSG00000102466 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14169
FGF16GeneProductENSG00000196468 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:80903
FGF17GeneProductENSG00000158815 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14171
FGF18GeneProductENSG00000156427 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14172
FGF19GeneProductENSG00000162344 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14170
FGF1GeneProductENSG00000113578 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14164
FGF20GeneProductENSG00000078579 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:80857
FGF21GeneProductENSG00000105550 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:56636
FGF22GeneProductENSG00000070388 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:67112
FGF23GeneProductENSG00000118972 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:64654
FGF2GeneProductENSG00000138685 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14173
FGF3GeneProductENSG00000186895 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14174
FGF4GeneProductENSG00000075388 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14175
FGF5GeneProductENSG00000138675 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14176
FGF6GeneProductENSG00000111241 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14177
FGF7GeneProductENSG00000140285 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14178
FGF8GeneProductENSG00000107831 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14179
FGF9GeneProductENSG00000102678 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14180
FGFR1GeneProductENSG00000077782 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14182
FGFR2GeneProductENSG00000066468 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14183
FGFR3GeneProductENSG00000068078 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14184
FGFR4GeneProductENSG00000160867 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14186
FOSGeneProductENSG00000170345 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14281
FZD1GeneProductENSG00000157240 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14362
FZD2GeneProductENSG00000180340 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:57265
FZD3GeneProductENSG00000104290 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14365
FZD4GeneProductENSG00000174804 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14366
FZD5GeneProductENSG00000163251 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14367
FZD6GeneProductENSG00000164930 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14368
FZD7GeneProductENSG00000155760 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14369
FZD8GeneProductENSG00000177283 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14370
FZD9GeneProductENSG00000188763 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14371
GAB1GeneProductENSG00000109458 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14388
GDPMetaboliteHMDB0000960 (HMDB)
GRB2GeneProductENSG00000177885 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14784
GSK3BGeneProductENSG00000082701 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:56637
GTPMetaboliteHMDB0001440 (HMDB)
HNF1AGeneProductENSG00000135100 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:21405
HRASGeneProductENSG00000174775 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:15461
IKKProtein
IL6STGeneProductENSG00000134352 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16195
JAK1GeneProductENSG00000162434 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16451
JUNGeneProductENSG00000177606 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16476
LIFGeneProductENSG00000128342 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16878
LIFRGeneProductENSG00000113594 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16880
LRP5GeneProductENSG00000162337 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16973
LRP6GeneProductENSG00000070018 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16974
MAP2K1GeneProductENSG00000169032 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:26395
MAP2K2GeneProductENSG00000126934 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:26396
MAP2K3GeneProductENSG00000034152 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:26397
MAP2K5GeneProductENSG00000137764 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:23938
MAP2K6GeneProductENSG00000108984 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:26399
MAPK12GeneProductENSG00000188130 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:29857
MAPK1GeneProductENSG00000100030 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:26413
MAPK4GeneProductENSG00000141639 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:225724
MAPK6GeneProductENSG00000069956 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:50772
MAPK7GeneProductENSG00000166484 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:23939
MDM2GeneProductENSG00000135679 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:17246
MTORGeneProductENSG00000198793 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:56717
MycGeneProductNo homologues found for original id L:17869
NOGGeneProductENSG00000183691 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18121
PDGFAGeneProductENSG00000197461 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18590
PDGFBGeneProductENSG00000100311 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18591
PDGFRAGeneProductENSG00000134853 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18595
PDGFRBGeneProductENSG00000113721 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18596
PIK3CDGeneProductENSG00000171608 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18707
PIK3R2GeneProductENSG00000105647 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18709
PIP2MetaboliteQ27088398 (Wikidata)
PIP3MetaboliteHMDB0004249 (HMDB)
PTENGeneProductENSG00000171862 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:19211
PTPN11GeneProductENSG00000179295 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:19247
RAF1GeneProductENSG00000132155 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:110157
SELENOPGeneProductENSG00000250722 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:20363
SMAD1GeneProductENSG00000170365 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:17125
SMAD4GeneProductENSG00000141646 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:17128
SMAD5GeneProductENSG00000113658 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:17129
SMAD6GeneProductENSG00000137834 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:17130
SMAD7GeneProductENSG00000101665 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:17131
SMAD9GeneProductENSG00000120693 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:55994
SOS1GeneProductENSG00000115904 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:20662
STAT3GeneProductENSG00000168610 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:20848
WNT10AGeneProductENSG00000135925 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22409
WNT10BGeneProductENSG00000169884 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22410
WNT11GeneProductENSG00000085741 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22411
WNT16GeneProductENSG00000002745 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:93735
WNT1GeneProductENSG00000125084 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22408
WNT2BGeneProductENSG00000134245 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22414
WNT2GeneProductENSG00000105989 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22413
WNT3AGeneProductENSG00000154342 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22416
WNT3GeneProductENSG00000108379 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22415
WNT4GeneProductENSG00000162552 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22417
WNT5AGeneProductENSG00000114251 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22418
WNT5BGeneProductENSG00000111186 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22419
WNT6GeneProductENSG00000115596 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22420
WNT7AGeneProductENSG00000154764 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22421
WNT7BGeneProductENSG00000188064 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22422
WNT9BGeneProductENSG00000158955 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22412

Annotated Interactions

No annotated interactions
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