Wnt Signaling Pathway Netpath (Homo sapiens)

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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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Bibliography

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History

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CompareRevisionActionTimeUserComment
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
28125view19:12, 27 January 2009KhanspersRemoved Netpath suffix from name
22584view13:36, 14 November 2008Thomaschanged title (was duplicate of WP428)
21439view11:31, 14 November 2008MaintBot[[Pathway:Homo sapiens:Wnt NetPath 8]] moved to [[Pathway:WP363]]: Moved to stable identifier
14174view22:56, 21 May 2008AlexanderPicoModified categories
11945view23:29, 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

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