Wnt signaling (Homo sapiens)

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55, 513122, 213, 382251, 568161, 189, 428, 464, 522115, 47747758, 47755, 7050992, 385, 420, 428, 464...364, 37158288436, 4779, 55, 44329, 538Ca2+WntDestruction complexFrizzledreleasePIP2LRP5BCL9AXIN1CTNNB1LRP6RAC1RHOACSNK1G1CCND1LRP6NFATC2MTORDVL1DVL3CDK6MYCSOX1PI4K2APRKCACSNK1ECSNK1A1GCKRGSK3ARYKCTNNB1AKT1AXIN2ROR1CCND1CTBP1TSC1TCF3PRKCGTCF7L2MAP3K7ARRB2LEF1DVL1PPARGCSNK1DFRAT1APCMAPK2TEKTCF4DVL2PIP5K1BPRKCBGJA1PP361, 477477, 504504311, 50374, 195121, 132, 138, 155, 160...GSK3BROR2MAPK9202MAPK8169, 288, 386102, 477MAP3K7277, 286P275205, 295205TSC2403, 477397, 47774, 195, 304, 416, 533451175NLKEnzyme complexInhibitionAuto catalysisTransportPositive regulation of gene expressionLeads to through unknown mechanismNegative regulation of gene expressionTranslocation UbiquitinationDeubiquitinationSumoylationInduced catalysisProtein-protein interactionAcetylationDephosphorylationLEGENDPhosphorylationProteinmRNAProteinReceptorLigandDeacetylationGolgi apparatusEndosomeNucleusMitochondrionDesumoylationMethylationDemethylationPalmitoylationCytoplasmECPlasma membraneMTEndoplasmic reticulumCYPMGONUExtracellularERENProteolytic cleavageWnt Signaling PathwayCYNUCYNU


Description

WNT signal, through the canonical pathway, controls cell fate determination and through the non-canonical pathway controls cell movement and tissue polarity (Katoh et al). The name "wnt" is a fusion of two terms, wg derived from the Drosophila gene wingless (wg) and int derived from the proto-oncogene integration-1, which is the mammalian homolog of wg (Wend et al).

ß-catenin is the key regulated effector of Wnt, involved in canonical signaling (Cadigan et al). Free ß-catenin is bound by a multiprotein "destruction complex". The ß-catenin destruction complex is comprised of ß-catenin, scaffold proteins (APC, AXIN) and serine/threonine kinases that phosphorylate ß-catenin casein kinase 1 (CSNK1A1, CSNK1D, CSNK1E, CSNK1G1) and GSK3B (Katoh et al, Cadigan et al, Sakanaka et al). The sequential phosphorylation of ß-catenin by casein kinase 1 and GSK3 is recognised by an SCF-class E3-ubiquitin ligase, which targets it for polyubiquitination and proteosomal destruction (Cadigan et al).

Canonical WNT signals are transduced through a two-part receptor, a seven-transmembrane Frizzled (FZD) and low density lipoprotein receptor-related protein 5/6 (LRP5/LRP6) to a ß-catenin (CTNNB1) signaling cascade (Katoh et al, Wend et al, Bhanot et al, Pinson et al). On recruitment of deshevelled (DVL1) to FZD and AXIN to LRP6, ß-catenin destruction complex disassembles leading to its stabilization and nuclear accumulation (Katoh et al, Gao et al). Nuclear ß-catenin binds to T-cell factor/lymphoid enhancer factor (TCF/LEF) family of transcription factors and Legless family docking protein, BCL9. These activate the transcription of Wnt target genes CCND1, MYC(Katoh et al, Cadigan et al, Pinson et al, Rubinfeld et al, Kramps et al).

Non-canonical WNT signaling diverges downstream after being transduced through FZD family receptors and co-receptors, ROR2 and RYK. This pathway does not involve ß-catenin-mediated gene expression. Small G proteins such as RAC1, RHOA and downstream effectors of RAC including JNK are DVL-dependant effector molecules of the non-canonical pathway (Katoh et al, Gao et al). These have been implicated in cytoskeletal rearrangement (1), dendrite growth (Gao et al, Rosso et al) and control of cell polarity and orientation (Gao et al). Nemo-like kinase (NLK) and nuclear factor of activated T cells (NFAT) are Ca2+-dependant effectors of the non-canonical pathway. NLK inhibits canonical pathway by phosphorylation of TCF/LEF family transcription factors. NFAT transcription factor is implicated in convergent extension during early embryogenesis and carcinogenic metastasis (Gao et al).

NetPath (http://www.netpath.org) is a collaborative effort between PandeyLab at Johns Hopkins University (http://pandeylab.igm.jhmi.edu) and Institute of Bioinformatics (http://www.ibioinformatics.org). This version of the pathway is available at NetSlim (http://www.netpath.org/netslim). If you use this pathway, please cite the NetPath website.

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Bibliography

  1. Kandasamy K, Mohan SS, Raju R, Keerthikumar S, Kumar GS, Venugopal AK, Telikicherla D, Navarro JD, Mathivanan S, Pecquet C, Gollapudi SK, Tattikota SG, Mohan S, Padhukasahasram H, Subbannayya Y, Goel R, Jacob HK, Zhong J, Sekhar R, Nanjappa V, Balakrishnan L, Subbaiah R, Ramachandra YL, Rahiman BA, Prasad TS, Lin JX, Houtman JC, Desiderio S, Renauld JC, Constantinescu SN, Ohara O, Hirano T, Kubo M, Singh S, Khatri P, Draghici S, Bader GD, Sander C, Leonard WJ, Pandey A; ''''; , PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
135215view04:00, 8 August 2024EweitzRestore state positions
135214view03:59, 8 August 2024EweitzRefine legend, economize layout
135213view03:55, 8 August 2024EweitzEconomize layout
129667view00:41, 22 May 2024EweitzModified title
126288view06:30, 20 April 2023EgonwLicense is CCZero
120695view12:55, 23 December 2021EweitzStandardize case
120668view01:15, 23 December 2021EweitzStandardize font, weight
117855view15:20, 22 May 2021EweitzModified title
116001view15:57, 28 March 2021EgonwCopied the NetPath paper to the literature list.
116000view15:56, 28 March 2021EgonwModified title
115982view18:10, 23 March 2021EgonwModified description
107433view06:44, 8 October 2019DeSlModified title
105470view05:17, 8 August 2019KhanspersModified description
97637view13:39, 31 May 2018Lorasimonsconnect line
97562view07:24, 25 May 2018Fehrhartadded citation
97561view07:22, 25 May 2018Fehrhartfixed lines
94887view18:04, 11 October 2017KhanspersModified title
78571view14:50, 7 January 2015MaintBotadded missing graphIds
70630view00:23, 20 August 2013MaintBotUpdated xrefs by Anatoly Urisman
70108view19:00, 12 July 2013MaintBotupdated to 2013 schema
68007view06:28, 29 June 2013EgonwAdded missing "Entrez Gene" data sources to Proteins with an identifier (ID confirmed via Entrez Gene)
67750view11:58, 26 June 2013DdiglesOntology Term : 'canonical Wnt signaling pathway' added !
62949view11:52, 5 May 2013MaintBotModified title
47977view14:34, 23 April 2012NetPathModified description
47854view17:27, 13 April 2012Sham.ukPeriodical save, work in progress
47851view17:17, 13 April 2012Sham.ukPeriodical save, work in progress
47850view17:07, 13 April 2012Sham.ukPeriodical save, work in progress
47849view16:57, 13 April 2012Sham.ukPeriodical save, work in progress
45009view17:40, 6 October 2011KhanspersOntology Term : 'Wnt signaling pathway' added !
44607view21:23, 21 September 2011KhanspersUpdating content to NetSlim
44606view21:22, 21 September 2011KhanspersUpdating content to NetSlim
44605view21:21, 21 September 2011KhanspersUpdating content to NetSlim
44121view20:51, 24 August 2011KhanspersReverted to version '23:40, 1 March 2011' by Khanspers
44016view22:39, 22 August 2011Khanspers
44010view22:11, 22 August 2011KhanspersModified description
44005view21:51, 22 August 2011KhanspersAdded category
44004view21:47, 22 August 2011KhanspersModified description
44003view21:40, 22 August 2011KhanspersModified description
44002view21:38, 22 August 2011Khanspersremoved GenMAPP comment
44001view21:37, 22 August 2011KhanspersModified description
44000view21:30, 22 August 2011KhanspersUpdating pathway from NetSlim
41151view23:40, 1 March 2011MaintBotRemoved redundant pathway information and comments
38067view20:10, 6 August 2010AlexanderPicoadded wnt9b and connected to database
38019view02:40, 30 July 2010ElgavishReverted to version '02:33, 30 July 2010' by Elgavish
38018view02:39, 30 July 2010ElgavishSpecify description
38017view02:33, 30 July 2010ElgavishPCP pathway
38016view02:27, 30 July 2010ElgavishPeriodical save, work in progress
35029view09:17, 11 February 2010Thomasremoved old genmapp comments (moved to description)
35021view09:11, 11 February 2010ThomasModified description
28127view19:35, 27 January 2009KhanspersReverted to version '13:36, 14 November 2008' by Khanspers

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AKT1GeneProduct207
APCGeneProduct324
ARRB2GeneProduct409
AXIN1GeneProduct8312
AXIN2GeneProduct8313 (Entrez Gene)
BCL9GeneProduct607
CCND1GeneProduct595
CCND1GeneProduct595 (Entrez Gene)
CDK6GeneProduct1021
CSNK1A1GeneProduct1452
CSNK1DGeneProduct1453
CSNK1EGeneProduct1454
CSNK1G1GeneProduct53944
CTBP1GeneProduct1487
CTNNB1GeneProduct1499
DVL1GeneProduct1855
DVL2GeneProduct1856
DVL3GeneProduct1857
FRAT1GeneProduct10023
GCKRGeneProduct2646
GJA1GeneProduct2697 (Entrez Gene)
GSK3AGeneProduct2931
GSK3BGeneProduct2932
LEF1GeneProduct51176
LRP5GeneProduct4041
LRP6GeneProduct4040
LigandGeneProduct7040 (Entrez Gene)
MAP3K7GeneProduct6885 (Entrez Gene)
MAPK2GeneProduct2011 (Entrez Gene)
MAPK8GeneProduct5599
MAPK9GeneProduct5600
MTORGeneProduct207 (Entrez Gene)
MYCGeneProduct4609 (Entrez Gene)
NFATC2GeneProduct4773
NLKGeneProduct51701
PI4K2AGeneProduct55361 (Entrez Gene)
PIP5K1BGeneProduct8395
PPARGGeneProduct5468
PRKCAGeneProduct5578
PRKCBGeneProduct5579
PRKCGGeneProduct5582
ProteinProtein5894 (Entrez Gene)
ProteinProtein
RAC1GeneProduct5879
RHOAGeneProduct387
ROR1GeneProduct4919
ROR2GeneProduct4920
RYKGeneProduct6259
ReceptorGeneProduct7040 (Entrez Gene)
SOX1GeneProduct6656
TCF3GeneProduct6929
TCF4GeneProduct6934
TCF7L2GeneProduct6934
TEKGeneProduct7010 (Entrez Gene)
TSC1GeneProduct7248 (Entrez Gene)
TSC2GeneProduct7249
mRNAProtein

Annotated Interactions

No annotated interactions

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