GNAQ pathways in port-wine stain (Homo sapiens)

From WikiPathways

Revision as of 20:22, 28 July 2024 by Eweitz (Talk | contribs)
(diff) ←Older revision | Current revision (diff) | Newer revision→ (diff)
Jump to: navigation, search
1G actinMEKEndothelial cellERKGPCRGNAQGDPPIP2G-gammaProliferation and survivalG-betaGNAQGTPPLCPI3KTRIOPDPK1AKTMTORPKCNFKB1RAF1MAP2K1MAPK1RHOARAC1AMOTYAP1PIP3YAP1AMOTF actinNucleusMAP2K2MAP2K3MAP2K4MAP2K5MAP2K6MAP2K7MAPK3


Description

Port-wine stains are caused by somatic, mosaic mutations in the GNAQ gene. The pathogenic variant is usually a p.R183Q (c.G548A) mutation in guanine nucleotide binding protein alpha subunit q (GNAQ), primarily expressed in endothelial cells. This pathway shows predicted downstream targets of GNAQ that have been implicated in cell proliferation and survival, which leads to angiogenesis and capillary overgrowth.

The resulting capillary malformation (CM) causes visibly pink, dark red, or purple discoloration of skin. Such "port wine stain" (PWS) of the skin is usually apparent at birth. It has a prevalence of 3-5 children per 1000 live births. PWS lesions, also known as nevus flammeus, are permanent but treatable by laser and topical therapies. In approximately 1 in 50,000 newborns, PWS is associated with Sturge-Weber syndrome (SWS), a more serious condition that has symptoms including glaucoma, seizures, and developmental delay.

This diagram is based on figure 2 in Van Trigt et al. (2022).

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Ontology Terms

 

Bibliography

  1. William K. Van Trigt, Kristen M. Kelly, Christopher C. W. Hughes; ''GNAQ mutations drive port wine birthmark-associated Sturge-Weber syndrome: A review of pathobiology, therapies, and current models''; Frontiers in Human Neuroscience, 2022 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
134879view20:22, 28 July 2024EweitzIncrease node size, as corresponding state font size cannot change
134878view20:21, 28 July 2024EweitzDecrease state font size
134877view20:19, 28 July 2024EweitzEconomize layout
134876view20:17, 28 July 2024EweitzEconomize layout
129342view09:20, 27 March 2024MkutmonOntology Term : 'disease pathway' added !
129341view09:19, 27 March 2024MkutmonOntology Term : 'signaling pathway' added !
128750view08:01, 21 February 2024EgonwWhen the identifier is not known, just leave the Xref empty
128061view22:36, 23 January 2024AlexanderPicoFixed relX 1.1 values to 1.0
128054view12:02, 23 January 2024EweitzModified description
128053view11:58, 23 January 2024EweitzModified description
128049view11:01, 23 January 2024EweitzEconomize layout
128043view02:52, 22 January 2024EweitzElaborate gene groups, link MEK to formal entry in HGNC
127959view14:08, 20 January 2024EweitzRefine arrows from GNAQ to mim-stimulation
127955view01:57, 20 January 2024EweitzAdd identifiers for MEK and ERK
127954view00:17, 20 January 2024EweitzRefine AMOT, fix YES1 -> YAP1
127953view22:55, 19 January 2024EweitzModified description
127952view22:53, 19 January 2024EweitzModified description
127951view22:53, 19 January 2024EweitzModified description
127950view22:52, 19 January 2024EweitzLabel cell type, nucleus
127949view22:48, 19 January 2024EweitzComplex GPCR, add GDP / GTP states
127948view22:13, 19 January 2024EweitzModified description
127947view13:56, 19 January 2024EweitzOntology Term : 'vascular disease' added !
127946view13:55, 19 January 2024EweitzOntology Term : 'capillary disease' added !
127945view13:52, 19 January 2024EweitzOntology Term : 'Sturge-Weber syndrome' added !
127944view13:51, 19 January 2024EweitzOntology Term : 'endothelial cell' added !
127943view13:51, 19 January 2024EweitzModified description
127942view13:51, 19 January 2024EweitzModified description
127941view13:50, 19 January 2024EweitzModified description
127940view13:47, 19 January 2024EweitzModified description
127939view13:44, 19 January 2024EweitzNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AKTGeneProductENSG00000142208 (Ensembl)
AMOTGeneProductENSG00000126016 (Ensembl)
G-beta GeneProductIPR016346 (InterPro)
G-gammaGeneProductIPR036284 (InterPro)
GNAQGeneProductENSG00000156052 (Ensembl)
GPCRProtein
MAP2K1GeneProductENSG00000169032 (Ensembl) "MEK" is an general enzyme that can be encoded by any of 7 genes, per Wikipedia:

MAP2K1 (a.k.a. MEK1) MAP2K2 (a.k.a. MEK2) MAP2K3 (a.k.a. MKK3) MAP2K4 (a.k.a. MKK4) MAP2K5 (a.k.a. MKK5) MAP2K6 (a.k.a. MKK6) MAP2K7 (a.k.a. MKK7)

Literature notes:

"No specific YAP inhibitors are currently in clinical use, however, Truong et al. demonstrated that combined therapy with trametinib MEK1/2 inhibition and the lysosome inhibitor chloroquine increased cytotoxicity while indirectly decreasing YAP nuclear localization and transcriptional activity (Feng et al., 2019; Truong et al., 2020). Other groups have proposed GNAQ overactivation of ERK1/2 or MEK1/2 as a driver of UM, but inhibitors of this pathway alone are typically insufficient to stop progression and the degree of MAPK activation is widely heterogeneous within tumor sites"
MAP2K2GeneProductENSG00000126934 (Ensembl) "MEK" is an general enzyme that can be encoded by any of 7 genes, per Wikipedia:

MAP2K1 (a.k.a. MEK1) MAP2K2 (a.k.a. MEK2) MAP2K3 (a.k.a. MKK3) MAP2K4 (a.k.a. MKK4) MAP2K5 (a.k.a. MKK5) MAP2K6 (a.k.a. MKK6) MAP2K7 (a.k.a. MKK7)

Literature notes:

"No specific YAP inhibitors are currently in clinical use, however, Truong et al. demonstrated that combined therapy with trametinib MEK1/2 inhibition and the lysosome inhibitor chloroquine increased cytotoxicity while indirectly decreasing YAP nuclear localization and transcriptional activity (Feng et al., 2019; Truong et al., 2020). Other groups have proposed GNAQ overactivation of ERK1/2 or MEK1/2 as a driver of UM, but inhibitors of this pathway alone are typically insufficient to stop progression and the degree of MAPK activation is widely heterogeneous within tumor sites"
MAP2K3GeneProductENSG00000034152 (Ensembl) "MEK" is an general enzyme that can be encoded by any of 7 genes, per Wikipedia:

MAP2K1 (a.k.a. MEK1) MAP2K2 (a.k.a. MEK2) MAP2K3 (a.k.a. MKK3) MAP2K4 (a.k.a. MKK4) MAP2K5 (a.k.a. MKK5) MAP2K6 (a.k.a. MKK6) MAP2K7 (a.k.a. MKK7)

Literature notes:

"No specific YAP inhibitors are currently in clinical use, however, Truong et al. demonstrated that combined therapy with trametinib MEK1/2 inhibition and the lysosome inhibitor chloroquine increased cytotoxicity while indirectly decreasing YAP nuclear localization and transcriptional activity (Feng et al., 2019; Truong et al., 2020). Other groups have proposed GNAQ overactivation of ERK1/2 or MEK1/2 as a driver of UM, but inhibitors of this pathway alone are typically insufficient to stop progression and the degree of MAPK activation is widely heterogeneous within tumor sites"
MAP2K4GeneProductENSG00000065559 (Ensembl) "MEK" is an general enzyme that can be encoded by any of 7 genes, per Wikipedia:

MAP2K1 (a.k.a. MEK1) MAP2K2 (a.k.a. MEK2) MAP2K3 (a.k.a. MKK3) MAP2K4 (a.k.a. MKK4) MAP2K5 (a.k.a. MKK5) MAP2K6 (a.k.a. MKK6) MAP2K7 (a.k.a. MKK7)

Literature notes:

"No specific YAP inhibitors are currently in clinical use, however, Truong et al. demonstrated that combined therapy with trametinib MEK1/2 inhibition and the lysosome inhibitor chloroquine increased cytotoxicity while indirectly decreasing YAP nuclear localization and transcriptional activity (Feng et al., 2019; Truong et al., 2020). Other groups have proposed GNAQ overactivation of ERK1/2 or MEK1/2 as a driver of UM, but inhibitors of this pathway alone are typically insufficient to stop progression and the degree of MAPK activation is widely heterogeneous within tumor sites"
MAP2K5GeneProductENSG00000137764 (Ensembl) "MEK" is an general enzyme that can be encoded by any of 7 genes, per Wikipedia:

MAP2K1 (a.k.a. MEK1) MAP2K2 (a.k.a. MEK2) MAP2K3 (a.k.a. MKK3) MAP2K4 (a.k.a. MKK4) MAP2K5 (a.k.a. MKK5) MAP2K6 (a.k.a. MKK6) MAP2K7 (a.k.a. MKK7)

Literature notes:

"No specific YAP inhibitors are currently in clinical use, however, Truong et al. demonstrated that combined therapy with trametinib MEK1/2 inhibition and the lysosome inhibitor chloroquine increased cytotoxicity while indirectly decreasing YAP nuclear localization and transcriptional activity (Feng et al., 2019; Truong et al., 2020). Other groups have proposed GNAQ overactivation of ERK1/2 or MEK1/2 as a driver of UM, but inhibitors of this pathway alone are typically insufficient to stop progression and the degree of MAPK activation is widely heterogeneous within tumor sites"
MAP2K6GeneProductENSG00000108984 (Ensembl) "MEK" is an general enzyme that can be encoded by any of 7 genes, per Wikipedia:

MAP2K1 (a.k.a. MEK1) MAP2K2 (a.k.a. MEK2) MAP2K3 (a.k.a. MKK3) MAP2K4 (a.k.a. MKK4) MAP2K5 (a.k.a. MKK5) MAP2K6 (a.k.a. MKK6) MAP2K7 (a.k.a. MKK7)

Literature notes:

"No specific YAP inhibitors are currently in clinical use, however, Truong et al. demonstrated that combined therapy with trametinib MEK1/2 inhibition and the lysosome inhibitor chloroquine increased cytotoxicity while indirectly decreasing YAP nuclear localization and transcriptional activity (Feng et al., 2019; Truong et al., 2020). Other groups have proposed GNAQ overactivation of ERK1/2 or MEK1/2 as a driver of UM, but inhibitors of this pathway alone are typically insufficient to stop progression and the degree of MAPK activation is widely heterogeneous within tumor sites"
MAP2K7GeneProductENSG00000076984 (Ensembl) "MEK" is an general enzyme that can be encoded by any of 7 genes, per Wikipedia:

MAP2K1 (a.k.a. MEK1) MAP2K2 (a.k.a. MEK2) MAP2K3 (a.k.a. MKK3) MAP2K4 (a.k.a. MKK4) MAP2K5 (a.k.a. MKK5) MAP2K6 (a.k.a. MKK6) MAP2K7 (a.k.a. MKK7)

Literature notes:

"No specific YAP inhibitors are currently in clinical use, however, Truong et al. demonstrated that combined therapy with trametinib MEK1/2 inhibition and the lysosome inhibitor chloroquine increased cytotoxicity while indirectly decreasing YAP nuclear localization and transcriptional activity (Feng et al., 2019; Truong et al., 2020). Other groups have proposed GNAQ overactivation of ERK1/2 or MEK1/2 as a driver of UM, but inhibitors of this pathway alone are typically insufficient to stop progression and the degree of MAPK activation is widely heterogeneous within tumor sites"
MAPK1GeneProductENSG00000100030 (Ensembl) Literature notes: "No specific YAP inhibitors are currently in clinical use, however, Truong et al. demonstrated that combined therapy with trametinib MEK1/2 inhibition and the lysosome inhibitor chloroquine increased cytotoxicity while indirectly decreasing YAP nuclear localization and transcriptional activity (Feng et al., 2019; Truong et al., 2020). Other groups have proposed GNAQ overactivation of ERK1/2 or MEK1/2 as a driver of UM, but inhibitors of this pathway alone are typically insufficient to stop progression and the degree of MAPK activation is widely heterogeneous within tumor sites"
MAPK3GeneProductENSG00000102882 (Ensembl) Literature notes: "No specific YAP inhibitors are currently in clinical use, however, Truong et al. demonstrated that combined therapy with trametinib MEK1/2 inhibition and the lysosome inhibitor chloroquine increased cytotoxicity while indirectly decreasing YAP nuclear localization and transcriptional activity (Feng et al., 2019; Truong et al., 2020). Other groups have proposed GNAQ overactivation of ERK1/2 or MEK1/2 as a driver of UM, but inhibitors of this pathway alone are typically insufficient to stop progression and the degree of MAPK activation is widely heterogeneous within tumor sites"
MTORGeneProductENSG00000198793 (Ensembl)
NFKB1GeneProductENSG00000109320 (Ensembl)
PDPK1GeneProductENSG00000152256 (Ensembl)
PI3KGeneProductENSG00000121879 (Ensembl)
PIP2Metabolite
PIP3Metabolite
PKCGeneProduct
PLCGeneProductPLC is a family of genes. The pathway diagram in the publication says "PLC". The publication text refers to PLC-gamma and PLC-beta, each of which is also a smaller gene family.

Literature notes: "There are a variety of well-defined downstream targets of G proteins, although their role in PWB is not understood. GNAQ in particular can stimulate the phospholipase C β (PLC-β) isoforms..."

"The exact mechanisms leading to hypertrophy and nodularity are not characterized, but Yin et al. (2017) identify upregulation of PP2A, DAG, and activation of PI3K, PKCα, PDPK1, and PLCγ in the patient tissue."
Proliferation and survivalPathway
RAC1GeneProductENSG00000136238 (Ensembl)
RAF1GeneProductENSG00000132155 (Ensembl)
RHOAGeneProductENSG00000067560 (Ensembl) https://doi.org/10.3390/cancers14133066 notes: "Feng et al. demonstrated that the GNAQ oncogene is able to control the Hippo pathway through a cytoplasmic protein tyrosine kinase called focal adhesion kinase (FAK). They detailed that Gαq activates FAK through a non-canonical TRIO-RhoA signalling pathway"
TRIOGeneProductENSG00000038382 (Ensembl)
YAP1GeneProductENSG00000137693 (Ensembl)

Annotated Interactions

No annotated interactions

Personal tools