WNT SIGNALING, THE PLANAR CELL POLARITY PATHWAY (PW:0000200)
Description
The planar cell polarity Wnt signaling pathway (PCP) plays a major role in embryonic tissue patterning, cell polarization, migration and morphogenesis. The PCP pathway, along with the Wnt-calcium pathway, belongs to the non-canonical Wnt signaling in that is independent of beta-catenin, the core component of the canonical Wnt pathway. The PCP pathway is less well understood and characterized but evidence is rapidly accumulating establishing the core components and the role they play, the common denominators and the distinctions between Drosophila and vertebrates. Frizzled receptors (Fzd) and the intracellular dishevelled (Dvl), the latter representing the branching point between canonical and non-canonical pathways, are necessary components. A requirement for Wnt ligands is controversial but some, like Wnt5, Wnt7 and Wnt11 appear to play a role, at least in vertebrates. Other core components include the membrane proteins Vangl2 (Strabismus/Van Gogh homolog) and Celsr1 (Flamingo homolog) and the cytoplasmic Prickle. Additional members of the vertebrate PCP pathway include Ptk7 and Scrib and the downstream effector Daam1. The asymmetric and polarized membrane association of PCP components has been established in Drosophila; a similar, yet distinct pattern has been observed in mammals. Scrib interacting with Vangl2 plays a role in the asymmetric positioning of Vangl2 (interaction mediated by the
PDZ domains of the two proteins, a domain also shared by the modular dishevelled); Celsr1 also contributes to the asymmetric localization of Vangl2. Ptk7 also appears to interact with Vangl2 but this interaction plays, remains to be established. Vangl can recruit Prickle which then can bind to and antagonize Dvl recruitment by Fzd. Activation of Fzd and recruitment of Dvl leads to activation of the members of the Rho family of small monomeric G proteins RhoA ¿ via interaction with Daam1, and Rac and subsequent triggering of Rho/Rac/Cdc42 and C-Jun N-terminal kinase (JNK) pathways. The former pathway controls cytoskeletal rearrangements and organization and the latter impacts on gene expression. Deregulation of the pathway has been implicated in a number of human diseases including cancer.
To see the ontology report for annotations, GViewer and download, click here [click to see the ontology report for related GO term -
GO:0060071 and KEGG map -
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Pathway Diagram:
Genes in Pathway:
G
Celsr1 cadherin, EGF LAG seven-pass G-type receptor 1
ISO RGD
PMID:17226800 RGD:2293492
NCBI chr 7:116,987,616...117,125,035
G
Daam1 dishevelled associated activator of morphogenesis 1
ISO RGD
PMID:17226800 RGD:2293492
NCBI chr 6:90,389,544...90,550,114
G
Dvl1 dishevelled segment polarity protein 1
ISO RGD
PMID:15608632 RGD:1581694
NCBI chr 5:166,456,989...166,468,733
G
Dvl2 dishevelled segment polarity protein 2
ISO RGD
PMID:17226800 RGD:2293492
NCBI chr10:54,723,356...54,732,823
G
Fzd3 frizzled class receptor 3
ISO RGD
PMID:17226800 RGD:2293492
NCBI chr15:39,421,366...39,488,369
G
Fzd6 frizzled class receptor 6
ISO RGD
PMID:17226800 RGD:2293492
NCBI chr 7:70,055,012...70,086,781
G
Prickle1 prickle planar cell polarity protein 1
ISO RGD
PMID:17226800 RGD:2293492
NCBI chr 7:124,639,142...124,735,027
G
Prickle2 prickle planar cell polarity protein 2
ISO RGD
PMID:17226800 RGD:2293492
NCBI chr 4:124,869,655...125,214,862
G
Ptk7 protein tyrosine kinase 7
ISO RGD
PMID:17226800 RGD:2293492
NCBI chr 9:14,352,155...14,418,473
G
Rac1 Rac family small GTPase 1
ISO RGD
PMID:15608632 RGD:1581694
NCBI chr12:11,037,028...11,057,251
G
Rhoa ras homolog family member A
ISO RGD
PMID:15637299 RGD:2302030
NCBI chr 8:108,991,926...109,025,746
G
Scrib scribble planar cell polarity protein
ISO RGD
PMID:17226800 RGD:2293492
NCBI chr 7:107,759,343...107,782,364
G
Vangl2 VANGL planar cell polarity protein 2
ISO RGD
PMID:17226800 RGD:2293492
NCBI chr13:84,462,731...84,489,404
G
Wnt7b Wnt family member 7B
ISO IMP RGD
PMID:15608632 PMID:18177422 RGD:1581694 , RGD:2292645
NCBI chr 7:116,634,817...116,679,459
Pathway Gene Annotations
Disease Annotations Associated with Genes in the Wnt signaling, the planar cell polarity pathway
Celsr1 genetic disease , hereditary lymphedema , intellectual disability , long QT syndrome , Lymphatic Malformation 9 , Phelan-McDermid syndrome , situs inversus , visceral heterotaxy , Walker-Warburg syndrome Daam1 epilepsy , genetic disease , intrinsic cardiomyopathy Dvl1 autosomal dominant Robinow syndrome 1 , autosomal dominant Robinow syndrome 2 , chromosome 1p36 deletion syndrome , congenital myasthenic syndrome 8 , DiGeorge syndrome , dilated cardiomyopathy 1LL , disease of mental health , Ehlers-Danlos syndrome spondylodysplastic type 2 , genetic disease , Goldberg-Shprintzen syndrome , idiopathic generalized epilepsy , immunodeficiency 16 , immunodeficiency 38 , Joubert syndrome 25 , myocardial infarction , Neurodevelopmental Disorders , Peroxisome Biogenesis Disorder, Complementation Group 7 , Robinow syndrome , Shprintzen-Goldberg Craniosynostosis Dvl2 common variable immunodeficiency , congenital myasthenic syndrome 2A , dextro-looped transposition of the great arteries , dyskeratosis congenita , genetic disease , intellectual disability , Li-Fraumeni syndrome , very long chain acyl-CoA dehydrogenase deficiency , Weissenbacher-Zweymuller syndrome Fzd3 Agenesis of Corpus Callosum , autosomal dominant nocturnal frontal lobe epilepsy , benign familial infantile seizures 6 , cerebellar hypoplasia , colorectal cancer , genetic disease , schizophrenia , Williams-Beuren syndrome Fzd6 amenorrhea , Cohen syndrome , genetic disease , Hydrops Fetalis , nail disease , nephroblastoma , nonsyndromic congenital nail disorder 1 Prickle1 autism spectrum disorder , autosomal recessive Robinow syndrome , benign epilepsy with centrotemporal spikes , epilepsy , fetal akinesia deformation sequence syndrome 1 , focal epilepsy , genetic disease , intellectual disability , progressive myoclonus epilepsy , progressive myoclonus epilepsy 1B , temporal lobe epilepsy , velocardiofacial syndrome , visual epilepsy Prickle2 autosomal dominant intellectual developmental disorder , benign epilepsy with centrotemporal spikes , epilepsy , genetic disease , Liver Neoplasms , Myoclonic Epilepsies , pre-malignant neoplasm , progressive myoclonus epilepsy , progressive myoclonus epilepsy 5 , sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Ptk7 genetic disease , infantile Refsum disease , Neurodevelopmental Disorders , Zellweger syndrome Rac1 autosomal dominant intellectual developmental disorder 48 , breast cancer , Cardiomegaly , Cardiotoxicity , colon adenocarcinoma , colon adenoma , colorectal adenocarcinoma , colorectal cancer , colorectal carcinoma , congestive heart failure , Developmental Disabilities , Developmental Disease , diabetes mellitus , dilated cardiomyopathy , extrahepatic bile duct adenocarcinoma , gallbladder carcinoma , gastric adenocarcinoma , genetic disease , head and neck squamous cell carcinoma , hepatocellular carcinoma , Left Ventricular Hypertrophy , liver disease , lung adenocarcinoma , lung cancer , melanoma , nasopharynx carcinoma , Neoplasm Metastasis , Neoplastic Cell Transformation , neurodevelopmental disorder with dysmorphic facies and distal limb anomalies , pancreatic adenocarcinoma , pancreatic ductal adenocarcinoma , Sepsis , skin melanoma , stomach cancer , uterine cancer , Ventricular Dysfunction, Left Rhoa Abnormalities, Drug-Induced , acute myocardial infarction , Aicardi-Goutieres Syndrome 1 , alopecia , Animal Disease Models , asthma , Brain Injuries , breast cancer , breast carcinoma , Breast Neoplasms , carcinoma , Cardiomegaly , Cocaine-Related Disorders , colorectal cancer , Colorectal Neoplasms , congenital diaphragmatic hernia , Craniofacial Abnormalities , Diabetic Nephropathies , ectodermal dysplasia , ECTODERMAL DYSPLASIA WITH FACIAL DYSMORPHISM AND ACRAL, OCULAR, AND BRAIN ANOMALIES , esophageal carcinoma , Experimental Autoimmune Encephalomyelitis , Experimental Autoimmune Neuritis , Experimental Diabetes Mellitus , Experimental Liver Cirrhosis , fetal alcohol syndrome , Fibrosis , gastric adenocarcinoma , genetic disease , Germ Cell and Embryonal Neoplasms , glycine encephalopathy , head and neck squamous cell carcinoma , hypertension , Hypopigmentation , Immunoblastic Lymphadenopathy , Left Ventricular Hypertrophy , Leukoencephalopathies , lung adenocarcinoma , Lymphatic Metastasis , membranous glomerulonephritis , multiple sclerosis , Myocardial Reperfusion Injury , Neoplasm Invasiveness , Neoplasm Metastasis , Neurocutaneous Syndromes , non-Hodgkin lymphoma , obesity , Optic Nerve Injuries , ovarian carcinoma , peripheral T-cell lymphoma , Pierson syndrome , primary cutaneous T-cell non-Hodgkin lymphoma , proteinuria , pulmonary hypertension , Spinal Cord Injuries , Stomach Neoplasms , T-cell non-Hodgkin lymphoma , tooth disease , urinary bladder cancer , Urologic Neoplasms , withdrawal disorder Scrib Brown-Vialetto-Van Laere syndrome 2 , epidermolysis bullosa simplex with muscular dystrophy , genetic disease , holoprosencephaly , microcephaly , neural tube defect Vangl2 autoimmune interstitial lung, joint, and kidney disease , gastrointestinal stromal tumor , genetic disease , Kidney Neoplasms , neural tube defect , parathyroid carcinoma , spina bifida Wnt7b breast cancer , breast fibroadenoma , Experimental Mammary Neoplasms , genetic disease , intellectual disability , Phelan-McDermid syndrome , syndromic microphthalmia 5 , syndromic microphthalmia 9 , urinary bladder cancer
Abnormalities, Drug-Induced Rhoa acute myocardial infarction Rhoa Agenesis of Corpus Callosum Fzd3 Aicardi-Goutieres Syndrome 1 Rhoa alopecia Rhoa amenorrhea Fzd6 Animal Disease Models Rhoa asthma Rhoa autism spectrum disorder Prickle1 autoimmune interstitial lung, joint, and kidney disease Vangl2 autosomal dominant intellectual developmental disorder Prickle2 autosomal dominant intellectual developmental disorder 48 Rac1 autosomal dominant nocturnal frontal lobe epilepsy Fzd3 autosomal dominant Robinow syndrome 1 Dvl1 autosomal dominant Robinow syndrome 2 Dvl1 autosomal recessive Robinow syndrome Prickle1 benign epilepsy with centrotemporal spikes Prickle1 , Prickle2 benign familial infantile seizures 6 Fzd3 Brain Injuries Rhoa breast cancer Rac1 , Rhoa , Wnt7b breast carcinoma Rhoa breast fibroadenoma Wnt7b Breast Neoplasms Rhoa Brown-Vialetto-Van Laere syndrome 2 Scrib carcinoma Rhoa Cardiomegaly Rac1 , Rhoa Cardiotoxicity Rac1 cerebellar hypoplasia Fzd3 chromosome 1p36 deletion syndrome Dvl1 Cocaine-Related Disorders Rhoa Cohen syndrome Fzd6 colon adenocarcinoma Rac1 colon adenoma Rac1 colorectal adenocarcinoma Rac1 colorectal cancer Fzd3 , Rac1 , Rhoa colorectal carcinoma Rac1 Colorectal Neoplasms Rhoa common variable immunodeficiency Dvl2 congenital diaphragmatic hernia Rhoa congenital myasthenic syndrome 2A Dvl2 congenital myasthenic syndrome 8 Dvl1 congestive heart failure Rac1 Craniofacial Abnormalities Rhoa Developmental Disabilities Rac1 Developmental Disease Rac1 dextro-looped transposition of the great arteries Dvl2 diabetes mellitus Rac1 Diabetic Nephropathies Rhoa DiGeorge syndrome Dvl1 dilated cardiomyopathy Rac1 dilated cardiomyopathy 1LL Dvl1 disease of mental health Dvl1 dyskeratosis congenita Dvl2 ectodermal dysplasia Rhoa ECTODERMAL DYSPLASIA WITH FACIAL DYSMORPHISM AND ACRAL, OCULAR, AND BRAIN ANOMALIES Rhoa Ehlers-Danlos syndrome spondylodysplastic type 2 Dvl1 epidermolysis bullosa simplex with muscular dystrophy Scrib epilepsy Daam1 , Prickle1 , Prickle2 esophageal carcinoma Rhoa Experimental Autoimmune Encephalomyelitis Rhoa Experimental Autoimmune Neuritis Rhoa Experimental Diabetes Mellitus Rhoa Experimental Liver Cirrhosis Rhoa Experimental Mammary Neoplasms Wnt7b extrahepatic bile duct adenocarcinoma Rac1 fetal akinesia deformation sequence syndrome 1 Prickle1 fetal alcohol syndrome Rhoa Fibrosis Rhoa focal epilepsy Prickle1 gallbladder carcinoma Rac1 gastric adenocarcinoma Rac1 , Rhoa gastrointestinal stromal tumor Vangl2 genetic disease Celsr1 , Daam1 , Dvl1 , Dvl2 , Fzd3 , Fzd6 , Prickle1 , Prickle2 , Ptk7 , Rac1 , Rhoa , Scrib , Vangl2 , Wnt7b Germ Cell and Embryonal Neoplasms Rhoa glycine encephalopathy Rhoa Goldberg-Shprintzen syndrome Dvl1 head and neck squamous cell carcinoma Rac1 , Rhoa hepatocellular carcinoma Rac1 hereditary lymphedema Celsr1 holoprosencephaly Scrib Hydrops Fetalis Fzd6 hypertension Rhoa Hypopigmentation Rhoa idiopathic generalized epilepsy Dvl1 Immunoblastic Lymphadenopathy Rhoa immunodeficiency 16 Dvl1 immunodeficiency 38 Dvl1 infantile Refsum disease Ptk7 intellectual disability Celsr1 , Dvl2 , Prickle1 , Wnt7b intrinsic cardiomyopathy Daam1 Joubert syndrome 25 Dvl1 Kidney Neoplasms Vangl2 Left Ventricular Hypertrophy Rac1 , Rhoa Leukoencephalopathies Rhoa Li-Fraumeni syndrome Dvl2 liver disease Rac1 Liver Neoplasms Prickle2 long QT syndrome Celsr1 lung adenocarcinoma Rac1 , Rhoa lung cancer Rac1 Lymphatic Malformation 9 Celsr1 Lymphatic Metastasis Rhoa melanoma Rac1 membranous glomerulonephritis Rhoa microcephaly Scrib multiple sclerosis Rhoa myocardial infarction Dvl1 Myocardial Reperfusion Injury Rhoa Myoclonic Epilepsies Prickle2 nail disease Fzd6 nasopharynx carcinoma Rac1 Neoplasm Invasiveness Rhoa Neoplasm Metastasis Rac1 , Rhoa Neoplastic Cell Transformation Rac1 nephroblastoma Fzd6 neural tube defect Scrib , Vangl2 Neurocutaneous Syndromes Rhoa neurodevelopmental disorder with dysmorphic facies and distal limb anomalies Rac1 Neurodevelopmental Disorders Dvl1 , Ptk7 non-Hodgkin lymphoma Rhoa nonsyndromic congenital nail disorder 1 Fzd6 obesity Rhoa Optic Nerve Injuries Rhoa ovarian carcinoma Rhoa pancreatic adenocarcinoma Rac1 pancreatic ductal adenocarcinoma Rac1 parathyroid carcinoma Vangl2 peripheral T-cell lymphoma Rhoa Peroxisome Biogenesis Disorder, Complementation Group 7 Dvl1 Phelan-McDermid syndrome Celsr1 , Wnt7b Pierson syndrome Rhoa pre-malignant neoplasm Prickle2 primary cutaneous T-cell non-Hodgkin lymphoma Rhoa progressive myoclonus epilepsy Prickle1 , Prickle2 progressive myoclonus epilepsy 1B Prickle1 progressive myoclonus epilepsy 5 Prickle2 proteinuria Rhoa pulmonary hypertension Rhoa Robinow syndrome Dvl1 schizophrenia Fzd3 sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Prickle2 Sepsis Rac1 Shprintzen-Goldberg Craniosynostosis Dvl1 situs inversus Celsr1 skin melanoma Rac1 spina bifida Vangl2 Spinal Cord Injuries Rhoa stomach cancer Rac1 Stomach Neoplasms Rhoa syndromic microphthalmia 5 Wnt7b syndromic microphthalmia 9 Wnt7b T-cell non-Hodgkin lymphoma Rhoa temporal lobe epilepsy Prickle1 tooth disease Rhoa urinary bladder cancer Rhoa , Wnt7b Urologic Neoplasms Rhoa uterine cancer Rac1 velocardiofacial syndrome Prickle1 Ventricular Dysfunction, Left Rac1 very long chain acyl-CoA dehydrogenase deficiency Dvl2 visceral heterotaxy Celsr1 visual epilepsy Prickle1 Walker-Warburg syndrome Celsr1 Weissenbacher-Zweymuller syndrome Dvl2 Williams-Beuren syndrome Fzd3 withdrawal disorder Rhoa Zellweger syndrome Ptk7
