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 7:118,867,450...119,004,859
G
Daam1
dishevelled associated activator of morphogenesis 1
ISO
RGD
PMID:17226800 RGD:2293492
NCBI chr 6:96,125,521...96,286,049
G
Dvl1
dishevelled segment polarity protein 1
ISO
RGD
PMID:15608632 RGD:1581694
NCBI chr 5:171,738,911...171,750,967
G
Dvl2
dishevelled segment polarity protein 2
ISO
RGD
PMID:17226800 RGD:2293492
NCBI chr10:55,222,245...55,231,506
G
Fzd3
frizzled class receptor 3
ISO
RGD
PMID:17226800 RGD:2293492
NCBI chr15:43,596,962...43,664,047
G
Fzd6
frizzled class receptor 6
ISO
RGD
PMID:17226800 RGD:2293492
NCBI chr 7:71,939,916...71,971,685
G
Prickle1
prickle planar cell polarity protein 1
ISO
RGD
PMID:17226800 RGD:2293492
NCBI chr 7:126,518,587...126,614,581
G
Prickle2
prickle planar cell polarity protein 2
ISO
RGD
PMID:17226800 RGD:2293492
NCBI chr 4:126,426,767...126,771,986
G
Ptk7
protein tyrosine kinase 7
ISO
RGD
PMID:17226800 RGD:2293492
NCBI chr 9:21,849,756...21,916,077
G
Rac1
Rac family small GTPase 1
ISO
RGD
PMID:15608632 RGD:1581694
NCBI chr12:16,150,411...16,170,864
G
Rhoa
ras homolog family member A
ISO
RGD
PMID:15637299 RGD:2302030
NCBI chr 8:117,870,548...117,904,303
G
Scrib
scribble planar cell polarity protein
ISO
RGD
PMID:17226800 RGD:2293492
NCBI chr 7:109,640,034...109,663,354
G
Vangl2
VANGL planar cell polarity protein 2
ISO
RGD
PMID:17226800 RGD:2293492
NCBI chr13:86,995,124...87,021,770
G
Wnt7b
Wnt family member 7B
ISO IMP
RGD
PMID:15608632 PMID:18177422 RGD:1581694 , RGD:2292645
NCBI chr 7:118,514,684...118,559,316
Pathway Gene Annotations
Disease Annotations Associated with Genes in the Wnt signaling, the planar cell polarity pathway
Celsr1 bladder exstrophy-epispadias-cloacal exstrophy complex , long QT syndrome , Lymphatic Malformation 9 , visceral heterotaxy , visceral heterotaxy 5 , Walker-Warburg syndrome , yellow nail syndrome Daam1 epilepsy , intrinsic cardiomyopathy Dvl1 autosomal dominant Robinow syndrome 1 , autosomal dominant Robinow syndrome 2 , Desbuquois dysplasia , DiGeorge syndrome , disease of mental health , genetic disease , myocardial infarction , Robinow syndrome Dvl2 dextro-looped transposition of the great arteries Fzd3 Agenesis of Corpus Callosum , cerebellar hypoplasia , colorectal cancer , schizophrenia , Williams-Beuren syndrome Fzd6 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 , Experimental Seizures , fetal akinesia deformation sequence syndrome 1 , genetic disease , intellectual disability , progressive myoclonus epilepsy , progressive myoclonus epilepsy 1B , temporal lobe epilepsy , velocardiofacial syndrome Prickle2 autosomal dominant intellectual developmental disorder , benign epilepsy with centrotemporal spikes , epilepsy , Liver Neoplasms , Myoclonic Epilepsies , pre-malignant neoplasm , progressive myoclonus epilepsy , progressive myoclonus epilepsy 5 , sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Ptk7 Neurodevelopmental Disorders 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 , hepatocellular carcinoma , left ventricular failure , 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 , stomach cancer Rhoa Abnormalities, Drug-Induced , acute myocardial infarction , alopecia , Animal Disease Models , asthma , Brain Injuries , breast cancer , breast carcinoma , carcinoma , Cardiomegaly , Cocaine-Related Disorders , colorectal cancer , congenital diaphragmatic hernia , Craniofacial Abnormalities , Diabetic Nephropathies , ectodermal dysplasia , ECTODERMAL DYSPLASIA WITH FACIAL DYSMORPHISM AND ACRAL, OCULAR, AND BRAIN ANOMALIES , Experimental Autoimmune Encephalomyelitis , Experimental Autoimmune Neuritis , Experimental Diabetes Mellitus , Experimental Liver Cirrhosis , fetal alcohol syndrome , Fibrosis , genetic disease , Germ Cell and Embryonal Neoplasms , hypertension , Hypopigmentation , Immunoblastic Lymphadenopathy , Left Ventricular Hypertrophy , Leukoencephalopathies , Lymphatic Metastasis , membranous glomerulonephritis , multiple sclerosis , Myocardial Reperfusion Injury , Neoplasm Invasiveness , Neoplasm Metastasis , Neurocutaneous Syndromes , obesity , Optic Nerve Injuries , ovarian carcinoma , peripheral T-cell lymphoma , primary biliary cholangitis , 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 microcephaly , neural tube defect Vangl2 genetic disease , Kidney Neoplasms , neural tube defect , spina bifida Wnt7b breast cancer , breast fibroadenoma , Experimental Mammary Neoplasms , syndromic microphthalmia 5 , syndromic microphthalmia 9 , urinary bladder cancer
Abnormalities, Drug-Induced Rhoa acute myocardial infarction Rhoa Agenesis of Corpus Callosum Fzd3 alopecia Rhoa Animal Disease Models Rhoa asthma Rhoa autism spectrum disorder Prickle1 autosomal dominant intellectual developmental disorder Prickle2 autosomal dominant intellectual developmental disorder 48 Rac1 autosomal dominant Robinow syndrome 1 Dvl1 autosomal dominant Robinow syndrome 2 Dvl1 autosomal recessive Robinow syndrome Prickle1 benign epilepsy with centrotemporal spikes Prickle1 , Prickle2 bladder exstrophy-epispadias-cloacal exstrophy complex Celsr1 Brain Injuries Rhoa breast cancer Rac1 , Rhoa , Wnt7b breast carcinoma Rhoa breast fibroadenoma Wnt7b carcinoma Rhoa Cardiomegaly Rac1 , Rhoa Cardiotoxicity Rac1 cerebellar hypoplasia Fzd3 Cocaine-Related Disorders Rhoa colon adenocarcinoma Rac1 colon adenoma Rac1 colorectal adenocarcinoma Rac1 colorectal cancer Fzd3 , Rac1 , Rhoa colorectal carcinoma Rac1 congenital diaphragmatic hernia Rhoa congestive heart failure Rac1 Craniofacial Abnormalities Rhoa Desbuquois dysplasia Dvl1 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 disease of mental health Dvl1 ectodermal dysplasia Rhoa ECTODERMAL DYSPLASIA WITH FACIAL DYSMORPHISM AND ACRAL, OCULAR, AND BRAIN ANOMALIES Rhoa epilepsy Daam1 , Prickle1 , Prickle2 Experimental Autoimmune Encephalomyelitis Rhoa Experimental Autoimmune Neuritis Rhoa Experimental Diabetes Mellitus Rhoa Experimental Liver Cirrhosis Rhoa Experimental Mammary Neoplasms Wnt7b Experimental Seizures Prickle1 extrahepatic bile duct adenocarcinoma Rac1 fetal akinesia deformation sequence syndrome 1 Prickle1 fetal alcohol syndrome Rhoa Fibrosis Rhoa gallbladder carcinoma Rac1 gastric adenocarcinoma Rac1 genetic disease Dvl1 , Fzd6 , Prickle1 , Rac1 , Rhoa , Vangl2 Germ Cell and Embryonal Neoplasms Rhoa hepatocellular carcinoma Rac1 Hydrops Fetalis Fzd6 hypertension Rhoa Hypopigmentation Rhoa Immunoblastic Lymphadenopathy Rhoa intellectual disability Prickle1 intrinsic cardiomyopathy Daam1 Kidney Neoplasms Vangl2 left ventricular failure Rac1 Left Ventricular Hypertrophy Rac1 , Rhoa Leukoencephalopathies Rhoa liver disease Rac1 Liver Neoplasms Prickle2 long QT syndrome Celsr1 lung adenocarcinoma Rac1 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 Ptk7 nonsyndromic congenital nail disorder 1 Fzd6 obesity Rhoa Optic Nerve Injuries Rhoa ovarian carcinoma Rhoa pancreatic adenocarcinoma Rac1 pancreatic ductal adenocarcinoma Rac1 peripheral T-cell lymphoma Rhoa pre-malignant neoplasm Prickle2 primary biliary cholangitis Rhoa 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 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 velocardiofacial syndrome Prickle1 visceral heterotaxy Celsr1 visceral heterotaxy 5 Celsr1 Walker-Warburg syndrome Celsr1 Williams-Beuren syndrome Fzd3 withdrawal disorder Rhoa yellow nail syndrome Celsr1
