Wnt Signaling Pathway (Homo sapiens)

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Wnt Frizzled PIP2 CSNK1E CSNK1A1 CSNK1D CSNK1G1 Destruction complex 2+ release Ca DVL3 AKT1 FRAT1 MAPK1 GJA1 ARRB2 GCKR CTBP1 MYC CTNNB1 TEK AXIN2 TSC1 MAP3K7 LRP5 PPARG CTNNB1 DVL2 TCF7L2 NFATC2 MTOR CCND1 SOX1 AXIN1 APC P GSK3A GSK3B P DVL1 DVL1 PRKCA PRKCB PRKCG RHOA RAC1 CCND1 CDK6 TCF3 LEF1 BCL9 TCF4 PI4K2A PIP5K1B RYK ROR1 ROR2 LRP6 LRP6 MAPK9 P MAPK8 P MAP3K7 TSC2 NLK Inhibition Auto catalysis Transport Positive regulation of gene expression Leads to through unknown mechanism Negative regulation of gene expression Translocation Ubiquitination Deubiquitination Sumoylation Induced catalysis Protein-protein interaction Acetylation Dephosphorylation LEGEND Phosphorylation Deacetylation Golgi apparatus Endosome Nucleus Mitochondrion Desumoylation Methylation Demethylation Palmitoylation Cytoplasm EC Plasma membrane MT Endoplasmic reticulum CY PM GO NU Extracellular ER EN Proteolytic cleavage Wnt Signaling Pathway CY NU CY NU mRNA Receptor Ligand Protein Enzyme complex Protein Name: Wnt Signaling Pathway License: Freely available under Creative Commons license Organism: Homo sapiens


Description

WNT signal, through the canonical pathway, controls cell fate determination and through the non-canonical pathway controls cell movement and tissue polarity. 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. ß-catenin is the key regulated effector of Wnt, involved in canonical signaling . 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. 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. 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. On recruitment of deshevelled (DVL1) to FZD and AXIN to LRP6, ß-catenin destruction complex disassembles leading to its stabilization and nuclear accumulation. 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. 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. These have been implicated in cytoskeletal rearrangement, dendrite growth and control of cell polarity and orientation. 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.

Please access this pathway at NetSlim database.

If you use this pathway, you must cite following paper: Kandasamy, K., Mohan, S. S., Raju, R., Keerthikumar, S., Kumar, G. S. S., Venugopal, A. K., Telikicherla, D., Navarro, J. D., Mathivanan, S., Pecquet, C., Gollapudi, S. K., Tattikota, S. G., Mohan, S., Padhukasahasram, H., Subbannayya, Y., Goel, R., Jacob, H. K. C., Zhong, J., Sekhar, R., Nanjappa, V., Balakrishnan, L., Subbaiah, R., Ramachandra, Y. L., Rahiman, B. A., Prasad, T. S. K., Lin, J., Houtman, J. C. D., Desiderio, S., Renauld, J., Constantinescu, S. N., Ohara, O., Hirano, T., Kubo, M., Singh, S., Khatri, P., Draghici, S., Bader, G. D., Sander, C., Leonard, W. J. and Pandey, A. (2010). NetPath: A public resource of curated signal transduction pathways. Genome Biology. 11:R3.

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Ontology Terms

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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

History

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RevisionActionTimeUserComment
97637view 06:39, 31 May 2018Lorasimonsconnect line
97562view 00:24, 25 May 2018Fehrhartadded citation
97561view 00:22, 25 May 2018Fehrhartfixed lines
94887view 11:04, 11 October 2017KhanspersModified title
78571view 07:50, 7 January 2015MaintBotadded missing graphIds
70630view 17:23, 19 August 2013MaintBotUpdated xrefs by Anatoly Urisman
70108view 12:00, 12 July 2013MaintBotupdated to 2013 schema
68007view 23:28, 28 June 2013EgonwAdded missing "Entrez Gene" data sources to Proteins with an identifier (ID confirmed via Entrez Gene)
67750view 04:58, 26 June 2013DdiglesOntology Term : 'canonical Wnt signaling pathway' added !
62949view 04:52, 5 May 2013MaintBotModified title
47977view 07:34, 23 April 2012NetPathModified description
47854view 10:27, 13 April 2012Sham.ukPeriodical save, work in progress
47851view 10:17, 13 April 2012Sham.ukPeriodical save, work in progress
47850view 10:07, 13 April 2012Sham.ukPeriodical save, work in progress
47849view 09:57, 13 April 2012Sham.ukPeriodical save, work in progress
45009view 10:40, 6 October 2011KhanspersOntology Term : 'Wnt signaling pathway' added !
44607view 14:23, 21 September 2011KhanspersUpdating content to NetSlim
44606view 14:22, 21 September 2011KhanspersUpdating content to NetSlim
44605view 14:21, 21 September 2011KhanspersUpdating content to NetSlim
44121view 13:51, 24 August 2011KhanspersReverted to version '23:40, 1 March 2011' by Khanspers
44016view 15:39, 22 August 2011Khanspers
44010view 15:11, 22 August 2011KhanspersModified description
44005view 14:51, 22 August 2011KhanspersAdded category
44004view 14:47, 22 August 2011KhanspersModified description
44003view 14:40, 22 August 2011KhanspersModified description
44002view 14:38, 22 August 2011Khanspersremoved GenMAPP comment
44001view 14:37, 22 August 2011KhanspersModified description
44000view 14:30, 22 August 2011KhanspersUpdating pathway from NetSlim
41151view 16:40, 1 March 2011MaintBotRemoved redundant pathway information and comments
38067view 13:10, 6 August 2010AlexanderPicoadded wnt9b and connected to database
38019view 19:40, 29 July 2010ElgavishReverted to version '02:33, 30 July 2010' by Elgavish
38018view 19:39, 29 July 2010ElgavishSpecify description
38017view 19:33, 29 July 2010ElgavishPCP pathway
38016view 19:27, 29 July 2010ElgavishPeriodical save, work in progress
35029view 02:17, 11 February 2010Thomasremoved old genmapp comments (moved to description)
35021view 02:11, 11 February 2010ThomasModified description
28127view 12:35, 27 January 2009KhanspersReverted to version '13:36, 14 November 2008' by Khanspers
28125view 12:12, 27 January 2009KhanspersRemoved Netpath suffix from name
22584view 06:36, 14 November 2008Thomaschanged title (was duplicate of WP428)
21439view 04:31, 14 November 2008MaintBot[[Pathway:Homo sapiens:Wnt NetPath 8]] moved to [[Pathway:WP363]]: Moved to stable identifier
14174view 15:56, 21 May 2008AlexanderPicoModified categories
11945view 16:29, 12 May 2008KhanspersNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AKT1Protein207 (Entrez Gene)
APCProtein324 (Entrez Gene)
ARRB2Protein409 (Entrez Gene)
AXIN1Protein8312 (Entrez Gene)
AXIN2Rna8313 (Entrez Gene)
BCL9Protein607 (Entrez Gene)
CCND1Rna595 (Entrez Gene)
CDK6Protein1021 (Entrez Gene)
CSNK1A1Protein1452 (Entrez Gene)
CSNK1DProtein1453 (Entrez Gene)
CSNK1EProtein1454 (Entrez Gene)
CSNK1G1Protein53944 (Entrez Gene)
CTBP1Protein1487 (Entrez Gene)
CTNNB1Protein1499 (Entrez Gene)
DVL1Protein1855 (Entrez Gene)
DVL2Protein1856 (Entrez Gene)
DVL3Protein1857 (Entrez Gene)
FRAT1Protein10023 (Entrez Gene)
GCKRProtein2646 (Entrez Gene)
GJA1Rna2697 (Entrez Gene)
GSK3AProtein2931 (Entrez Gene)
GSK3BProtein2932 (Entrez Gene)
LEF1Protein51176 (Entrez Gene)
LRP5Protein4041 (Entrez Gene)
LRP6Protein4040 (Entrez Gene)
MAP3K7Protein6885 (Entrez Gene)
MAPK1Protein5594 (Entrez Gene)
MAPK8Protein5599 (Entrez Gene)
MAPK9Protein5601 (Entrez Gene)
MTORProtein2475 (Entrez Gene)
MYCRna4609 (Entrez Gene)
NFATC2Protein4773 (Entrez Gene)
NLKProtein51701 (Entrez Gene)
PI4K2AProtein55361 (Entrez Gene)
PIP5K1BProtein8395 (Entrez Gene)
PPARGProtein5468 (Entrez Gene)
PRKCAProtein5578 (Entrez Gene)
PRKCBProtein5579 (Entrez Gene)
PRKCGProtein5582 (Entrez Gene)
RAC1Protein5879 (Entrez Gene)
RHOAProtein387 (Entrez Gene)
ROR1Protein4919 (Entrez Gene)
ROR2Protein4920 (Entrez Gene)
RYKProtein6259 (Entrez Gene)
SOX1Protein6656 (Entrez Gene)
TCF3Protein6929 (Entrez Gene)
TCF4Protein6925 (Entrez Gene)
TCF7L2Protein6934 (Entrez Gene)
TEKRna7010 (Entrez Gene)
TSC1Protein7248 (Entrez Gene)
TSC2Protein7249 (Entrez Gene)

Annotated Interactions

<cite>No annotated interactions</cite>