KEGG PATHWAY: ko04310

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

Module

M00380

SCF-BTRC complex [PATH:ko04310]

Disease

H00078	Frontotemporal lobar degeneration (FTLD)
H00450	Sclerosing bone dysplasias
H00451	Osteoporosis-pseudoglioma syndrome (OPPG)
H00589	Familial exudative vitreoretinopathy (FEVR)
H00598	46,XX disorders of sex development (Disorders of gonadal development)
H00600	46,XX disorders of sex development (Other)
H00607	46,XY disorders of sex development (Disorders of gonadal development)
H00625	Tooth agenesis
H00636	Tetra-amelia
H00646	Odontoonychodermal dysplasia
H00681	Acne inversa
H00810	Progressive myoclonic epilepsy (PME)
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 (NDNC)

Other DBs

BSID:

471

GO:

0016055

Orthology

K00181	porcupine
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
K01691	WNT inhibitory factor 1
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
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)
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
K04498	E1A/CREB-binding protein [EC:2.3.1.48]
K04499	RuvB-like protein 1 (pontin 52)
K04501	mothers against decapentaplegic homolog 4
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	cyclin D1
K10151	cyclin D2
K10152	cyclin D3
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:6.3.2.19]
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
K08110	glypican 4 (K-glypican)
K04510	vang-like
K04511	prickle
K04512	dishevelled associated activator of morphogenesis
K04513	Ras homolog gene family, member A
K04514	Rho-associated protein kinase [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	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	protein phosphatase 3, catalytic subunit [EC:3.1.3.16]
K06268	protein phosphatase 3, regulatory subunit
K02677	classical protein kinase C [EC:2.7.11.13]
K04446	nuclear factor of activated T-cells, cytoplasmic

Compound

C00076

Calcium cation

Reference

PMID:14635791

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)

Reference

PMID:14745971

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)

Reference

PMID:12446114

Authors

Kalderon D.

Title

Similarities between the Hedgehog and Wnt signaling pathways.

Journal

Trends Cell Biol 12:523-31 (2002)

Reference

PMID:14530294

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)

Reference

PMID:15102436

Authors

Jope RS, Johnson GV.

Title

The glamour and gloom of glycogen synthase kinase-3.

Journal

Trends Biochem Sci 29:95-102 (2004)

Reference

PMID:12967557

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)

Reference

PMID:11433294

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)

Reference

PMID:23256519

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)

Reference

PMID:19482104

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)

Reference

PMID:18838381

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)

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Ontology (2)   
   KEGG BRITE (1)   
   GO (1)   
Pathway (4)   
   KEGG PATHWAY (2)   
   KEGG MODULE (1)   
   BioSystems (1)   
Disease (23)   
   KEGG DISEASE (23)   
Chemical substance (1)   
   KEGG COMPOUND (1)   
Chemical reaction (15)   
   KEGG ENZYME (15)   
Gene (95)   
   KEGG ORTHOLOGY (95)   
Literature (10)   
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