Hippo-Merlin signaling dysregulation (WP4541)

Homo sapiens

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The Hippo-Merlin(NF2) signaling pathway can become dysregulated at many points as observed in malignant mesothelioma cells. Extracellular signals via cadherin, CD44, integrin or RTKs, as well as various signaling pathway components, can affect NF2 tumor suppression. Direct alteration of merlin and LATS1/2 can also result in underphosphorylated (activated) YAP1(YY1AP1)/TAZ transcriptional coactivators, leading to the induction of pro-oncogene expression. This pathway was created based on figure 1 from Sekido et al. Phosphorylation sites were added based on information from PhosphoSitePlus, www.phosphosite.org.

Authors

Alex Pico , Marvin Martens , Eric Weitz , and Kristina Hanspers

Activity

last edited

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Cited In

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Organisms

Homo sapiens

Communities

CPTAC Diseases Rare Diseases

Annotations

Pathway Ontology

Hippo signaling pathway disease pathway altered Hippo signaling pathway signaling pathway

Participants
Query Drugst.One

Label Type Compact URI Comment
CDH1 GeneProduct ncbigene:999 Cadherin
CDH10 GeneProduct ncbigene:1008 Cadherin
CDH11 GeneProduct ncbigene:1009 Cadherin
CDH12 GeneProduct ncbigene:1010 Cadherin
CDH13 GeneProduct ncbigene:1012 Cadherin
CDH15 GeneProduct ncbigene:1013 Cadherin
CDH16 GeneProduct ncbigene:1014 Cadherin
CDH17 GeneProduct ncbigene:1015 Cadherin
CDH18 GeneProduct ncbigene:1016 Cadherin
CDH19 GeneProduct ncbigene:28513 Cadherin
CDH2 GeneProduct ncbigene:1000 Cadherin
CDH20 GeneProduct ncbigene:28316 Cadherin
CDH22 GeneProduct ncbigene:64405 Cadherin
CDH24 GeneProduct ncbigene:64403 Cadherin
CDH3 GeneProduct ncbigene:1001 Cadherin
CDH4 GeneProduct ncbigene:1002 Cadherin
CDH5 GeneProduct ncbigene:1003 Cadherin
CDH6 GeneProduct ncbigene:1004 Cadherin
CDH7 GeneProduct ncbigene:1005 Cadherin
CDH8 GeneProduct ncbigene:1006 Cadherin
CDH9 GeneProduct ncbigene:1007 Cadherin
PRKACA GeneProduct ncbigene:5566 PKA
PRKACB GeneProduct ncbigene:5567 PKA
PRKACG GeneProduct ncbigene:5568 PKA
PRKAR1A GeneProduct ncbigene:5573 PKA
PRKAR2A GeneProduct ncbigene:5576 PKA
PRKAR2B GeneProduct ncbigene:5577 PKA
ITGA1 GeneProduct hgnc.symbol:ITGA1
ITGA2 GeneProduct hgnc.symbol:ITGA2
ITGA3 GeneProduct hgnc.symbol:ITGA3
ITGA4 GeneProduct hgnc.symbol:ITGA4
ITGA5 GeneProduct hgnc.symbol:ITGA5
ITGA6 GeneProduct hgnc.symbol:ITGA6
ITGA7 GeneProduct hgnc.symbol:ITGA7
ITGA8 GeneProduct hgnc.symbol:ITGA8
ITGA9 GeneProduct hgnc.symbol:ITGA9
ITGA10 GeneProduct hgnc.symbol:ITGA10
ITGA11 GeneProduct hgnc.symbol:ITGA11
ITGAD GeneProduct hgnc.symbol:ITGAD
ITGAE GeneProduct hgnc.symbol:ITGAE
ITGAL GeneProduct hgnc.symbol:ITGAL
ITGAM GeneProduct hgnc.symbol:ITGAM
ITGAV GeneProduct hgnc.symbol:ITGAV
ITGA2B GeneProduct hgnc.symbol:ITGA2B
ITGAX GeneProduct hgnc.symbol:ITGAX
ITGB1 GeneProduct hgnc.symbol:ITGB1
ITGB2 GeneProduct hgnc.symbol:ITGB2
ITGB3 GeneProduct hgnc.symbol:ITGB3
ITGB4 GeneProduct hgnc.symbol:ITGB4
ITGB5 GeneProduct hgnc.symbol:ITGB5
ITGB6 GeneProduct hgnc.symbol:ITGB6
ITGB7 GeneProduct hgnc.symbol:ITGB7
ITGB8 GeneProduct hgnc.symbol:ITGB8
PRKAR1B GeneProduct ncbigene:5575 PKA
LATS2 GeneProduct ncbigene:26524 LATS1/2
STK3 GeneProduct ncbigene:6788 MST1/2
LATS1 GeneProduct ncbigene:9113 LATS1/2
NF2 GeneProduct ncbigene:4771 Nf2
STK4 GeneProduct ncbigene:4485 MST1/2
TEAD1 GeneProduct ensembl:ENSG00000187079
YAP1 GeneProduct ncbigene:10413 YAP/TAZ
WWTR1 GeneProduct ncbigene:25937 YAP/TAZ
TEAD2 GeneProduct ensembl:ENSG00000074219
TEAD3 GeneProduct ensembl:ENSG00000007866
TEAD4 GeneProduct ensembl:ENSG00000197905
FGFR2 GeneProduct ensembl:ENSG00000066468 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14183
KDR GeneProduct ensembl:ENSG00000128052 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16542
INSR GeneProduct ensembl:ENSG00000171105 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16337
FGFR3 GeneProduct ensembl:ENSG00000068078 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14184
IGF1R GeneProduct ensembl:ENSG00000140443 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16001
KIT GeneProduct ensembl:ENSG00000157404 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16590
FGFR1 GeneProduct ensembl:ENSG00000077782 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14182
EPHA2 GeneProduct ensembl:ENSG00000142627 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:13836
EGFR GeneProduct ensembl:ENSG00000146648 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:13649
CSF1R GeneProduct ensembl:ENSG00000182578 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:12978
FGFR4 GeneProduct ensembl:ENSG00000160867 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14186
FLT1 GeneProduct ensembl:ENSG00000102755 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14254
FLT4 GeneProduct ensembl:ENSG00000037280 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14257
NGFR GeneProduct ensembl:ENSG00000064300 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18053
MET GeneProduct ensembl:ENSG00000105976 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:17295
PDGFRA GeneProduct ensembl:ENSG00000134853 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18595
PDGFRB GeneProduct ensembl:ENSG00000113721 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18596
TEK GeneProduct ensembl:ENSG00000120156 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:21687
FLT3 GeneProduct ensembl:ENSG00000122025 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14257
NTRK1 GeneProduct ensembl:ENSG00000198400 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:21687
NTRK2 GeneProduct ensembl:ENSG00000148053 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:21687
CXCL10 GeneProduct ncbigene:3627 MOB1
CD44 GeneProduct ncbigene:960 CD44
PAK5 GeneProduct ncbigene:57144 PAK,PKAMerlin
SAV1 GeneProduct ncbigene:60485 SAV1
PAK3 GeneProduct ncbigene:5063 PAK,PKAMerlin
PAK6 GeneProduct ncbigene:56924 PAK,PKAMerlin
PPP1R14A GeneProduct ncbigene:94274 CPI-17
CTNNB1 GeneProduct ncbigene:1499 β-cat
CCND1 GeneProduct ncbigene:595 CCND1,
MYC GeneProduct ncbigene:4609 MYC
PTK2 GeneProduct ncbigene:5747 FAK
PLCB4 GeneProduct ncbigene:5332 PLCB4
AMOT GeneProduct ncbigene:154796 AMOT
LIN28B GeneProduct ncbigene:389421 Lin28B
PAK4 GeneProduct ncbigene:10298 PAK,PKAMerlin
CTGF GeneProduct ncbigene:1490 CTGF
VGLL4 GeneProduct ncbigene:9686 VGLL4
NRAS GeneProduct ncbigene:4893 RAS
HRAS GeneProduct ncbigene:3265 RAS
PPP1R12A GeneProduct ncbigene:4659 MYPT-1
FOXM1 GeneProduct ncbigene:2305 FOXM1
PAK1 GeneProduct ncbigene:5058 PAK,PKAMerlin
AJUBA GeneProduct ncbigene:84962 AJUBA
PAK2 GeneProduct ncbigene:5062 PAK,PKAMerlin
KRAS GeneProduct ncbigene:3845 RAS
CTNNA1 GeneProduct ncbigene:1495 β-cat
LATS2 GeneProduct ncbigene:26524 LATS1/2
LATS1 GeneProduct ncbigene:9113 LATS1/2
NF2 GeneProduct ncbigene:4771 Nf2
MIR98 GeneProduct ncbigene:407054 Nf2
PPP1CA GeneProduct ncbigene:5499 MYPT-1
PPP1CB GeneProduct ncbigene:5500 MYPT-1
PPP1CC GeneProduct ncbigene:5501 MYPT-1
DCAF1 GeneProduct ncbigene:9730 Nf2
CUL4A GeneProduct ncbigene:8451 Nf2
DDB1 GeneProduct ncbigene:1642 Nf2
RBX1 GeneProduct ncbigene:9978 Nf2
YAP1 GeneProduct ncbigene:10413 YAP/TAZ
WWTR1 GeneProduct ncbigene:25937 YAP/TAZ

References

  1. Targeting the Hippo Pathway Is a New Potential Therapeutic Modality for Malignant Mesothelioma. Sekido Y. Cancers (Basel). 2018 Mar 22;10(4):90. PubMed Europe PMC Scholia