KEGG   PATHWAY: ko04310
Entry
ko04310                     Pathway                                

Name
Wnt signaling pathway
Description
Wnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, in many different species and organs. There are at least three different Wnt pathways: the canonical pathway, the planar cell polarity (PCP) pathway and the Wnt/Ca2+ pathway. In the canonical Wnt pathway, the major effect of Wnt ligand binding to its receptor is the stabilization of cytoplasmic beta-catenin through inhibition of the bea-catenin degradation complex. Beta-catenin is then free to enter the nucleus and activate Wnt-regulated genes through its interaction with TCF (T-cell factor) family transcription factors and concomitant recruitment of coactivators. Planar cell polarity (PCP) signaling leads to the activation of the small GTPases RHOA (RAS homologue gene-family member A) and RAC1, which activate the stress kinase JNK (Jun N-terminal kinase) and ROCK (RHO-associated coiled-coil-containing protein kinase 1) and leads to remodelling of the cytoskeleton and changes in cell adhesion and motility. WNT-Ca2+ signalling is mediated through G proteins and phospholipases and leads to transient increases in cytoplasmic free calcium that subsequently activate the kinase PKC (protein kinase C) and CAMKII (calcium calmodulin mediated kinase II) and the phosphatase calcineurin.
Class
Environmental Information Processing; Signal transduction
Pathway map
ko04310  Wnt signaling pathway
ko04310

Disease
H00078  Frontotemporal lobar degeneration
H00409  Type 2 diabetes mellitus
H00450  Worth type autosomal dominant osteosclerosis
H00451  Osteoporosis-pseudoglioma syndrome
H00485  Robinow syndrome
H00486  Sclerosteosis
H00589  Familial exudative vitreoretinopathy
H00600  Mullerian agenesis
H00625  Tooth agenesis
H00636  Tetra-amelia
H00646  Odontoonychodermal dysplasia
H00681  Acne inversa
H00857  Oligodontia-colorectal cancer syndrome
H00881  Li-Fraumeni syndrome
H00934  Caudal duplication anomaly
H00947  Pilomatricoma
H00949  Focal dermal hypoplasia
H00979  Caudal regression syndrome and Sirenomelia
H01007  Choroid plexus papilloma
H01023  Juvenile polyposis syndrome
H01025  Familial adenomatous polyposis
H01037  Vesicoureteral reflux
H01307  Nonsyndromic congenital nail disorder
H01667  Medulloblastoma
H01742  Coronary artery disease
H01774  Hyperostosis corticalis generalisata
H02102  Myhre syndrome
H02111  Autism
H02302  Hepatoblastoma
H02317  SERKAL syndrome
H02318  Palmoplantar hyperkeratosis with squamous cell carcinoma of skin and sex reversal
H02326  Keipert syndrome
Other DBs
GO: 0016055
Orthology
K00181  O-palmitoleoyl transferase [EC:2.3.1.250]
K03209  wingless-type MMTV integration site family, member 1
K00182  wingless-type MMTV integration site family, member 2
K00312  wingless-type MMTV integration site family, member 3
K00408  wingless-type MMTV integration site family, member 4
K00444  wingless-type MMTV integration site family, member 5
K00445  wingless-type MMTV integration site family, member 6
K00572  wingless-type MMTV integration site family, member 7
K00714  wingless-type MMTV integration site family, member 8
K01064  wingless-type MMTV integration site family, member 9
K01357  wingless-type MMTV integration site family, member 10
K01384  wingless-type MMTV integration site family, member 11
K01558  wingless-type MMTV integration site family, member 16
K01645  cerberus 1
K19882  O-palmitoleoyl-L-serine hydrolase [EC:3.1.1.98]
K01691  WNT inhibitory factor 1
K19614  pigment epithelium-derived factor
K16834  sclerostin
K02165  dickkopf
K02166  secreted frizzled-related protein 1
K02176  secreted frizzled-related protein 2
K02185  secreted frizzled-related protein 4
K02222  secreted frizzled-related protein 5
K02306  dally
K19471  R-spondin 1
K23097  R-spondin 2
K23098  R-spondin 3
K23099  R-spondin 4
K04309  leucine-rich repeat-containing G protein-coupled receptor 4
K04308  leucine-rich repeat-containing G protein-coupled receptor 5
K08399  leucine-rich repeat-containing G protein-coupled receptor 6
K15694  RING finger protein 43 [EC:2.3.2.27]
K16273  E3 ubiquitin-protein ligase ZNRF3 [EC:2.3.2.27]
K02432  frizzled 1/7
K02235  frizzled 2
K02329  frizzled 3
K02354  frizzled 4
K02375  frizzled 5/8
K02376  frizzled 6
K02842  frizzled 9/10
K04690  frizzled
K03068  low density lipoprotein receptor-related protein 5/6
K10162  BMP and activin membrane-bound inhibitor
K08960  casein kinase 1, epsilon [EC:2.7.11.1]
K02353  segment polarity protein dishevelled
K03069  frequently rearranged in advanced T-cell lymphomas 1
K03096  frequently rearranged in advanced T-cell lymphomas 2
K03097  casein kinase II subunit alpha [EC:2.7.11.1]
K03115  casein kinase II subunit beta
K03213  naked cuticle
K03344  Dvl-binding protein IDAX
K03345  sentrin-specific protease 2 (axin associating molecule) [EC:3.4.22.68]
K03083  glycogen synthase kinase 3 beta [EC:2.7.11.26]
K02105  catenin beta 1
K02157  axin 1
K04385  axin 2
K02085  adenomatosis polyposis coli protein
K08957  casein kinase 1, alpha [EC:2.7.11.1]
K02620  transcription factor 7
K04490  transcription factor 7-like 1
K04491  transcription factor 7-like 2
K04492  lymphoid enhancer-binding factor 1
K04493  beta-catenin-interacting protein 1 (inhibitor of beta-catenin and Tcf-4)
K23402  protein chibby 1
K04494  chromodomain helicase DNA binding protein 8 [EC:3.6.4.12]
K04495  transcription factor SOX17 (SOX group F)
K04496  C-terminal binding protein
K04497  groucho
K23491  catenin delta-2
K04498  E1A/CREB-binding protein [EC:2.3.1.48]
K04499  RuvB-like protein 1 (pontin 52)
K04501  mothers against decapentaplegic homolog 4
K23605  mothers against decapentaplegic homolog 3
K04427  mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25]
K04468  nemo like kinase [EC:2.7.11.24]
K04377  Myc proto-oncogene protein
K04448  transcription factor AP-1
K04502  fos-like antigen 1
K04503  G1/S-specific cyclin-D1
K10151  G1/S-specific cyclin-D2
K10152  G1/S-specific cyclin-D3
K22471  WNT1-inducible-signaling pathway protein 1
K04504  peroxisome proliferator-activated receptor delta
K01397  matrix metalloproteinase-7 (matrilysin, uterine) [EC:3.4.24.23]
K04505  presenilin 1 [EC:3.4.23.-]
K04345  protein kinase A [EC:2.7.11.11]
K04451  tumor protein p53
K04506  E3 ubiquitin-protein ligase SIAH1 [EC:2.3.2.27]
K04507  calcyclin binding protein
K03094  S-phase kinase-associated protein 1
K04508  transducin (beta)-like 1
K03362  F-box and WD-40 domain protein 1/11
K03347  cullin 1
K03868  RING-box protein 1 [EC:2.3.2.32]
K08110  glypican 4
K05122  receptor tyrosine kinase-like orphan receptor 1 [EC:2.7.10.1]
K05123  receptor tyrosine kinase-like orphan receptor 2 [EC:2.7.10.1]
K05128  RYK receptor-like tyrosine kinase [EC:2.7.10.1]
K04510  vang-like
K04511  prickle
K19626  inversin
K04512  dishevelled associated activator of morphogenesis
K04513  Ras homolog gene family, member A
K17388  Rho-associated protein kinase 2 [EC:2.7.11.1]
K04392  Ras-related C3 botulinum toxin substrate 1
K07860  Ras-related C3 botulinum toxin substrate 2
K07861  Ras-related C3 botulinum toxin substrate 3
K04440  mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24]
K05858  phosphatidylinositol phospholipase C, beta [EC:3.1.4.11]
K04515  calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17]
K04348  serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16]
K06268  serine/threonine-protein phosphatase 2B regulatory subunit
K02677  classical protein kinase C alpha type [EC:2.7.11.13]
K19662  classical protein kinase C beta type [EC:2.7.11.13]
K19663  classical protein kinase C gamma type [EC:2.7.11.13]
K04446  nuclear factor of activated T-cells, cytoplasmic 1
K17332  nuclear factor of activated T-cells, cytoplasmic 2
K17333  nuclear factor of activated T-cells, cytoplasmic 3
K17334  nuclear factor of activated T-cells, cytoplasmic 4
Compound
C00076  Calcium cation
Reference
  Authors
Hatsell S, Rowlands T, Hiremath M, Cowin P.
  Title
Beta-catenin and Tcfs in mammary development and cancer.
  Journal
J Mammary Gland Biol Neoplasia 8:145-58 (2003)
DOI:10.1023/A:1025944723047
Reference
  Authors
Yang Y.
  Title
Wnts and wing: Wnt signaling in vertebrate limb development and musculoskeletal morphogenesis.
  Journal
Birth Defects Res Part C Embryo Today 69:305-17 (2003)
DOI:10.1002/bdrc.10026
Reference
  Authors
Kalderon D.
  Title
Similarities between the Hedgehog and Wnt signaling pathways.
  Journal
Trends Cell Biol 12:523-31 (2002)
DOI:10.1016/S0962-8924(02)02388-7
Reference
  Authors
Nusse R.
  Title
Wnts and Hedgehogs: lipid-modified proteins and similarities in signaling mechanisms at the cell surface.
  Journal
Development 130:5297-305 (2003)
DOI:10.1242/dev.00821
Reference
  Authors
Jope RS, Johnson GV.
  Title
The glamour and gloom of glycogen synthase kinase-3.
  Journal
Trends Biochem Sci 29:95-102 (2004)
DOI:10.1016/j.tibs.2003.12.004
Reference
  Authors
Veeman MT, Axelrod JD, Moon RT.
  Title
A second canon. Functions and mechanisms of beta-catenin-independent Wnt signaling.
  Journal
Dev Cell 5:367-77 (2003)
DOI:10.1016/S1534-5807(03)00266-1
Reference
  Authors
Sun TQ, Lu B, Feng JJ, Reinhard C, Jan YN, Fantl WJ, Williams LT.
  Title
PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signalling.
  Journal
Nat Cell Biol 3:628-36 (2001)
DOI:10.1038/35083016
Reference
  Authors
Saito-Diaz K, Chen TW, Wang X, Thorne CA, Wallace HA, Page-McCaw A, Lee E
  Title
The way Wnt works: Components and mechanism.
  Journal
Growth Factors 31:1-31 (2013)
DOI:10.3109/08977194.2012.752737
Reference
  Authors
Carethers JM
  Title
Intersection of transforming growth factor-beta and Wnt signaling pathways in colorectal cancer and metastasis.
  Journal
Gastroenterology 137:33-6 (2009)
DOI:10.1053/j.gastro.2009.05.011
Reference
  Authors
Lin Z, Gao C, Ning Y, He X, Wu W, Chen YG
  Title
The pseudoreceptor BMP and activin membrane-bound inhibitor positively modulates Wnt/beta-catenin signaling.
  Journal
J Biol Chem 283:33053-8 (2008)
DOI:10.1074/jbc.M804039200
Reference
  Authors
Niehrs C
  Title
The complex world of WNT receptor signalling.
  Journal
Nat Rev Mol Cell Biol 13:767-79 (2012)
DOI:10.1038/nrm3470
Reference
  Authors
Abou Ziki MD, Mani A
  Title
Wnt signaling, a novel pathway regulating blood pressure? State of the art review.
  Journal
Atherosclerosis 262:171-178 (2017)
DOI:10.1016/j.atherosclerosis.2017.05.001
Reference
  Authors
He Y, Ki H, Kim H, Kim K
  Title
delta-Catenin interacts with LEF-1 and negatively regulates its transcriptional activity.
  Journal
Cell Biol Int 39:954-61 (2015)
DOI:10.1002/cbin.10465
Related
pathway
ko04010  MAPK signaling pathway
ko04110  Cell cycle
ko04115  p53 signaling pathway
ko04120  Ubiquitin mediated proteolysis
ko04350  TGF-beta signaling pathway
ko04510  Focal adhesion
ko04520  Adherens junction
ko05010  Alzheimer disease
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