Wnt Signaling Pathway Netpath (Bos taurus)

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PIP2CareleaseDestruction complex2+FrizzledWntDVL2LEF1AXIN2APCCCND1GCKRTEKCCND1MTORCTNNB1GSK3ATCF7L2CSNK1DCTNNB1AKT1LRP5PPARGCSNK1G1TSC1SOX1DVL1CDK6TCF3RYKGJA1RAC1PRKCBTCFL2FRAT1LRP6PI4K2AAXIN1MYCDVL3MAP3K7MAPK1CTBP1PRKCGNFATC2ARRB2DVL1PRKCARHOAROR1BCL9LRP6CSNK1EPIP5K1BCSNK1A1PPGSK3BROR2MAPK9MAPK8PMAP3K7PTSC2NLKInhibitionAuto catalysisTransportPositive regulation of gene expressionLeads to through unknown mechanismNegative regulation of gene expressionTranslocation UbiquitinationDeubiquitinationSumoylationInduced catalysisProtein-protein interactionAcetylationDephosphorylationLEGENDPhosphorylationDeacetylationGolgi apparatusEndosomeNucleusMitochondrionDesumoylationMethylationDemethylationPalmitoylationCytoplasmECPlasma membraneMTEndoplasmic reticulumCYPMGONUExtracellularERENProteolytic cleavageWnt Signaling PathwayCYNUCYNUmRNAReceptorLigandProteinEnzyme complexProtein


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.

Comments

HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP363(78571) with a 98.0% conversion rate.

Quality Tags

Ontology Terms

 

Bibliography

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History

View all...
CompareRevisionActionTimeUserComment
80668view15:21, 30 June 2015Mkutmonhomology conversion
63375view23:07, 9 May 2013MaintBotUpdated to 2013 gpml schema
40547view19:31, 1 March 2011MaintBotRemoved redundant pathway information and comments
35032view09:18, 11 February 2010Thomasremoved old genmapp comments (moved to description)
35024view09:14, 11 February 2010ThomasModified description
33787view00:11, 9 December 2009MaintBotAutomatic update of empty xrefs
31637view22:24, 13 August 2009MaintBotFixed text labels
30549view21:59, 29 July 2009MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
AKT1ProteinENSBTAG00000017636 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:207
APCProteinENSBTAG00000018852 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:324
ARRB2ProteinENSBTAG00000035587 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:409
AXIN1ProteinENSBTAG00000016577 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8312
AXIN2RnaENSBTAG00000030162 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8313
BCL9ProteinENSBTAG00000002422 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:607
CCND1RnaENSBTAG00000017514 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:595
CDK6ProteinENSBTAG00000044023 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1021
CSNK1A1Protein
CSNK1DProteinENSBTAG00000019986 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1453
CSNK1EProteinENSBTAG00000047582 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1454
CSNK1G1ProteinENSBTAG00000016823 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:53944
CTBP1ProteinENSBTAG00000008480 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1487
CTNNB1ProteinENSBTAG00000016420 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1499
DVL1ProteinENSBTAG00000010696 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1855
DVL2ProteinENSBTAG00000003075 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1856
DVL3ProteinENSBTAG00000019336 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1857
FRAT1ProteinENSBTAG00000007956 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10023
GCKRProteinENSBTAG00000031302 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2646
GJA1RnaENSBTAG00000001835 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2697
GSK3AProteinENSBTAG00000020756 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2931
GSK3BProteinENSBTAG00000048057 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2932
LEF1ProteinENSBTAG00000006844 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:51176
LRP5ProteinENSBTAG00000005903 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4041
LRP6ProteinENSBTAG00000011761 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4040
MAP3K7ProteinENSBTAG00000002625 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6885
MAPK1ProteinENSBTAG00000010312 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5594
MAPK8ProteinENSBTAG00000007876 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5599
MAPK9ProteinENSBTAG00000004709 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5601
MTORProteinENSBTAG00000015325 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2475
MYCRnaENSBTAG00000008409 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4609
NFATC2ProteinENSBTAG00000018270 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4773
NLKProteinENSBTAG00000014825 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:51701
PI4K2AProteinENSBTAG00000002010 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:55361
PIP5K1BProteinENSBTAG00000009917 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8395
PPARGProteinENSBTAG00000001333 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5468
PRKCAProteinENSBTAG00000001061 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5578
PRKCBProteinENSBTAG00000020921 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5579
PRKCGProteinENSBTAG00000013550 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5582
RAC1ProteinENSBTAG00000009233 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5879
RHOAProteinENSBTAG00000004279 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:387
ROR1ProteinENSBTAG00000012312 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4919
ROR2ProteinENSBTAG00000005092 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4920
RYKProteinENSBTAG00000016999 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6259
SOX1ProteinENSBTAG00000038272 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6656
TCF3ProteinENSBTAG00000008695 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6929
TCF7L2ProteinENSBTAG00000016462 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6925
TCFL2ProteinENSBTAG00000021574 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6934
TEKRnaENSBTAG00000020148 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7010
TSC1ProteinENSBTAG00000005190 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7248
TSC2ProteinENSBTAG00000020617 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7249

Annotated Interactions

No annotated interactions
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