Wnt signaling pathway and pluripotency (Homo sapiens)

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2473+p+pNucleusRecruitment to UnknownUbiquitin Conjugating EnzymeTRTRFrizzled LigandsPhosphorylated beta-cateninWnt ReceptorsProtein Kinase CPromotes PluripotencyPluripotencyTR: Transcriptional RegulationUbiquitin Taggedbeta-cateninStabilized beta-cateninDifferentiationbeta-cateninCytoskeletonTRTRbeta-cateninTRPP2A+pPromotes DifferentiationTcf/Lef-1TRTcf/Lef-1WNT5BCCND3DVL1LRP5FOXD3RACGAP1PRKCB1PRKCENLKWNT10BMAPK10FRAT1PPP2R2CFZD2NFYAPRKCDLRP6PLAUTCF7L2FZD3TCF7L1CCND1WNT5ATCF7WNT7BPRKCAPOU5F1GSK3BMMP7NKD1ZBTB33FZD1AXIN2FZD10WNT4GrouchoWNT1PPP2R5EPPP2R1ALEF1WNT10AFZD4PrkccWNT2BAXIN1FOSL1MAP3K7CD44APCPRKCHNANOGCCND2WNT16FZD7FZD9FZD5PPP2R5CLDLRPPP2CBWNT6RHOAPRKD1MAPK9BIOCBPCSNK1ECTBP1CTNND1WNT2PPP2R2BPPP2CADVL226S Proteasome DegradationP300FZD6CTBP2IQ-1TP53PRKCQPPP2R3BCTNNB1SOX2PPARDPRKCZJUNPPP2R4WNT3NKD2ApoptosisMAP2K4MYCPPM1JPRKCIPPP2R2AWNT3APPP2R3ADVL3FBXW2WNT9BWNT11WNT11PAFAH1B1PPP2R1BWNT7AFZD8ESRRBLRRK2-mut16


This pathway was adapted from several resources and is designed to provide a theoretical frame-work for examining Wnt signaling and interacting components in the context of embryonic stem-cell pluripotency and self-renewal.

A central organizing theme of this pathway are known drug targets which promote self-renewal or pluripotency (BIO and IQ-1) and implicated upstream regulators of the core pluripotency transcriptional components (e.g. Nanog). It should be noted that it is unclear whether all the depicted components participate in this pathway in human embryonic stem cells. Interactions and object/gene groups for the pathway exist for the majority of components.

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Ontology Terms



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  1. Pereira L, Yi F, Merrill BJ; ''Repression of Nanog gene transcription by Tcf3 limits embryonic stem cell self-renewal.''; Mol Cell Biol, 2006 PubMed Europe PMC Scholia
  2. ''Kegg version of this pathway''; http://www.genome.jp/kegg/pathway/hsa/hsa04310.html,
  3. Yi F, Pereira L, Merrill BJ; ''Tcf3 functions as a steady-state limiter of transcriptional programs of mouse embryonic stem cell self-renewal.''; Stem Cells, 2008 PubMed Europe PMC Scholia
  4. Chen CY, Weng YH, Chien KY, Lin KJ, Yeh TH, Cheng YP, Lu CS, Wang HL; ''(G2019S) LRRK2 activates MKK4-JNK pathway and causes degeneration of SN dopaminergic neurons in a transgenic mouse model of PD.''; Cell Death Differ, 2012 PubMed Europe PMC Scholia
  5. Sato N, Brivanlou AH; ''Manipulation of self-renewal in human embryonic stem cells through a novel pharmacological GSK-3 inhibitor.''; Methods Mol Biol, 2006 PubMed Europe PMC Scholia
  6. Zhang X, Zhang J, Wang T, Esteban MA, Pei D; ''''; , PubMed Europe PMC Scholia
  7. Miyabayashi T, Teo JL, Yamamoto M, McMillan M, Nguyen C, Kahn M; ''Wnt/beta-catenin/CBP signaling maintains long-term murine embryonic stem cell pluripotency.''; Proc Natl Acad Sci U S A, 2007 PubMed Europe PMC Scholia


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116550view12:49, 7 May 2021EweitzModified title
113990view09:33, 15 December 2020EgonwTwo more pathways clickable
105855view23:18, 15 August 2019KhanspersModified description
94890view19:09, 11 October 2017Khanspersfixed interactions
94866view19:00, 10 October 2017Khanspersfixed unconnected
94853view23:26, 9 October 2017KhanspersAdded cell shapes, updated layout for readability
90291view23:11, 2 November 2016AlexanderPicoOntology Term : 'PW:0000201' removed !
79474view12:28, 23 March 2015Zariadded Identifier for PrkCG
74897view22:14, 7 May 2014KhanspersUpdated state notation
68011view07:11, 29 June 2013EgonwAdded missing "WikiPathways" data sources for two pathways with WPxx identifiers.
68010view06:54, 29 June 2013EgonwFixed PubChem CID data source.
67757view11:59, 26 June 2013DdiglesOntology Term : 'canonical Wnt signaling pathway' added !
61692view22:45, 16 April 2013MaintBotremoved data source without identifer
59110view22:24, 21 February 2013MaintBotUpdated Ensembl and UniProt data source
58890view02:17, 21 February 2013NsalomonisSpecify description
58889view02:16, 21 February 2013NsalomonisAdded IDs for inhibitors and fixed beta-cat interactions
54212view22:40, 23 November 2012AlexanderPicoadded lrrk2
45007view17:36, 6 October 2011KhanspersModified description
45006view17:35, 6 October 2011KhanspersOntology Term : 'Wnt signaling pathway' added !
45005view17:34, 6 October 2011KhanspersOntology Term : 'pluripotent stem cell' added !
41060view23:17, 1 March 2011MaintBotRemoved redundant pathway information and comments
38957view00:51, 25 September 2010NsalomonisSpecify description
38788view00:26, 24 September 2010Khanspers
38680view17:36, 23 September 2010KhanspersAdded pathway links, changed T-bars to mim-inhibition, changed compartment graphics
38678view17:35, 23 September 2010KhanspersPeriodical save, work in progress
34645view21:35, 7 January 2010KhanspersFixed reference
34644view21:31, 7 January 2010KhanspersFixed reference
33653view19:28, 1 December 2009NsalomonisAdded ESRRB interactions
33649view18:59, 1 December 2009NsalomonisPeriodical save, work in progress
32419view17:08, 15 August 2009MaintBotFixed text labels
32076view13:38, 14 August 2009MaintBotFixed group labels
29616view12:15, 23 May 2009MartijnVanIerselUpdated ensembl references
29197view22:58, 10 April 2009AlexanderPicoFixed ID systems
29196view22:56, 10 April 2009AlexanderPicoFixed ID systems
21522view11:32, 14 November 2008MaintBot[[Pathway:Homo sapiens:Wnt signaling and pluripotency]] moved to [[Pathway:WP399]]: Moved to stable identifier
19854view02:34, 13 October 2008AlexanderPico
19645view17:41, 9 October 2008AlexanderPicotweak
19643view17:37, 9 October 2008AlexanderPicocopied fixes to groups and refs
14068view10:08, 21 May 2008MartijnVanIerselEdges connected
14065view10:04, 21 May 2008MartijnVanIerselPeriodical save, work in progress
10493view20:53, 2 February 2008NsalomonisIncluded additional Nanog interactions
8494view13:46, 7 January 2008MaintBot[[Pathway:Human:Wnt signaling and pluripotency]] moved to [[Pathway:Homo sapiens:Wnt signaling and pluripotency]]: Renaming species
7551view22:03, 13 December 2007Nsalomonisupdated
7549view03:40, 11 December 2007NsalomonisTcf protein IDs previously refered to mouse genes which have been renamed in human
7495view13:05, 4 November 2007Thomasadded kegg reference
7494view12:50, 4 November 2007Thomasadded to cellular process category
7191view12:31, 4 November 2007MaintBotAdded description to GPML
7185view21:15, 2 November 2007Nsalomonisadded a few lit refs
7182view20:32, 2 November 2007Nsalomonisminor
7180view18:11, 2 November 2007Nsalomonisminor

External references


View all...
NameTypeDatabase referenceComment
26S Proteasome DegradationPathwayWP183 (WikiPathways)
APCGeneProduct324 (Entrez Gene)
AXIN1GeneProduct8312 (Entrez Gene)
AXIN2GeneProduct8313 (Entrez Gene)
ApoptosisPathwayWP254 (WikiPathways)
BIOMetabolite5287844 (PubChem-compound)
CBPGeneProduct1387 (Entrez Gene)
CCND1GeneProduct595 (Entrez Gene)
CCND2GeneProduct894 (Entrez Gene)
CCND3GeneProduct896 (Entrez Gene)
CD44GeneProduct960 (Entrez Gene)
CSNK1EGeneProduct1454 (Entrez Gene)
CTBP1GeneProduct1487 (Entrez Gene)
CTBP2GeneProduct1488 (Entrez Gene)
CTNNB1GeneProduct1499 (Entrez Gene)
CTNND1GeneProduct1500 (Entrez Gene)
DVL1GeneProduct1855 (Entrez Gene)
DVL2GeneProduct1856 (Entrez Gene)
DVL3GeneProduct1857 (Entrez Gene)
ESRRBGeneProduct2103 (Entrez Gene)
FBXW2GeneProduct26190 (Entrez Gene)
FOSL1GeneProduct8061 (Entrez Gene)
FOXD3GeneProductENSG00000187140 (Ensembl)
FRAT1GeneProduct10023 (Entrez Gene)
FZD10GeneProductENSG00000111432 (Ensembl)
FZD1GeneProduct8321 (Entrez Gene)
FZD2GeneProduct2535 (Entrez Gene)
FZD3GeneProduct7976 (Entrez Gene)
FZD4GeneProduct8322 (Entrez Gene)
FZD5GeneProduct7855 (Entrez Gene)
FZD6GeneProduct8323 (Entrez Gene)
FZD7GeneProduct8324 (Entrez Gene)
FZD8GeneProduct8325 (Entrez Gene)
FZD9GeneProduct8326 (Entrez Gene)
GSK3BGeneProduct2932 (Entrez Gene)
IQ-1Metabolite331001-62-8 (CAS)
JUNGeneProduct3725 (Entrez Gene)
LDLRGeneProduct3949 (Entrez Gene)
LEF1GeneProduct51176 (Entrez Gene)
LRP5GeneProduct4041 (Entrez Gene)
LRP6GeneProduct4040 (Entrez Gene)
LRRK2-mutGeneProduct120892 (Entrez Gene)
MAP2K4GeneProduct6416 (Entrez Gene)
MAP3K7GeneProduct6885 (Entrez Gene)
MAPK10GeneProduct5602 (Entrez Gene)
MAPK9GeneProduct5601 (Entrez Gene)
MMP7GeneProduct4316 (Entrez Gene)
MYCGeneProduct4609 (Entrez Gene)
NANOGGeneProduct79923 (Entrez Gene)
NFYAGeneProductENSG00000001167 (Ensembl)
NKD1GeneProduct85407 (Entrez Gene)
NKD2GeneProduct85409 (Entrez Gene)
NLKGeneProduct51701 (Entrez Gene)
P300GeneProduct2033 (Entrez Gene)
PAFAH1B1GeneProduct5048 (Entrez Gene)
PLAUGeneProduct5328 (Entrez Gene)
POU5F1GeneProduct5460 (Entrez Gene)
PPARDGeneProduct5467 (Entrez Gene)
PPM1JGeneProductENSG00000155367 (Ensembl)
PPP2CAGeneProduct5515 (Entrez Gene)
PPP2CBGeneProduct5516 (Entrez Gene)
PPP2R1AGeneProduct5518 (Entrez Gene)
PPP2R1BGeneProduct5519 (Entrez Gene)
PPP2R2AGeneProduct5520 (Entrez Gene)
PPP2R2BGeneProduct5521 (Entrez Gene)
PPP2R2CGeneProduct5522 (Entrez Gene)
PPP2R3AGeneProduct5523 (Entrez Gene)
PPP2R3BGeneProduct28227 (Entrez Gene)
PPP2R4GeneProduct5524 (Entrez Gene)
PPP2R5CGeneProduct5527 (Entrez Gene)
PPP2R5EGeneProduct5529 (Entrez Gene)
PRKCAGeneProduct5578 (Entrez Gene)
PRKCB1GeneProduct5579 (Entrez Gene)
PRKCDGeneProduct5580 (Entrez Gene)
PRKCEGeneProduct5581 (Entrez Gene)
PRKCHGeneProduct5583 (Entrez Gene)
PRKCIGeneProduct5584 (Entrez Gene)
PRKCQGeneProduct5588 (Entrez Gene)
PRKCZGeneProduct5590 (Entrez Gene)
PRKD1GeneProduct5587 (Entrez Gene)
RACGAP1GeneProduct29127 (Entrez Gene)
RHOAGeneProduct387 (Entrez Gene)
SOX2GeneProduct6657 (Entrez Gene)
TCF7GeneProductENSG00000081059 (Ensembl)
TCF7L1GeneProduct83439 (Entrez Gene)
TCF7L2GeneProductENSG00000148737 (Ensembl)
TP53GeneProduct7157 (Entrez Gene)
WNT10AGeneProduct80326 (Entrez Gene)
WNT10BGeneProduct7480 (Entrez Gene)
WNT11GeneProduct7481 (Entrez Gene) Non-canonical Wnt signaling enhances differentiation of human circulating progenitor cells to cardiomyogenic cells. PMID: 15701629
WNT16GeneProduct51384 (Entrez Gene)
WNT1GeneProduct7471 (Entrez Gene)
WNT2GeneProduct7472 (Entrez Gene)
WNT2BGeneProduct7482 (Entrez Gene)
WNT3GeneProduct7473 (Entrez Gene)
WNT3AGeneProduct89780 (Entrez Gene)
WNT4GeneProduct54361 (Entrez Gene)
WNT5AGeneProduct7474 (Entrez Gene)
WNT5BGeneProduct81029 (Entrez Gene)
WNT6GeneProduct7475 (Entrez Gene)
WNT7AGeneProduct7476 (Entrez Gene)
WNT7BGeneProduct7477 (Entrez Gene)
WNT9BGeneProduct7484 (Entrez Gene)
ZBTB33GeneProduct10009 (Entrez Gene)

Annotated Interactions

No annotated interactions

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