Hippo-Merlin signaling dysregulation (Homo sapiens)

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1DegradationPro-oncogenic genesCadherinmicroRNAITGB8CDH11CDH5CDH20ITGB6CDH4ITGA2BPRKAR2AITGA7CDH24CDH6ITGAEITGALCDH9ITGB1CDH13ITGA8ITGA2PRKAR1BITGAXCDH3CDH12CDH8ITGAVCDH18PRKACBITGB5ITGB3CDH16CDH7ITGA11PRKAR2BITGA10CDH10CDH17CDH19CDH22ITGA9ITGB4CDH2PRKACAITGA1ITGA6ITGB2ITGADITGA3CDH15CDH1ITGB7ITGA4PRKAR1AITGAMITGA5PRKACGNucleusLATS2STK3PLATS1PNF2PSTK4PTEAD1YAP1WWTR1PPPPTEAD2TEAD3TEAD4FGFR2KDRINSRFGFR3IGF1RKITFGFR1EPHA2EGFRCSF1RFGFR4FLT1FLT4NGFRMETPDGFRAPDGFRBTEKRTKFLT3NTRK1NTRK2PKACXCL10CD44PAK5SAV1PAK3PAK6PPP1R14ACTNNB1CCND1MYCPTK2PLCB4AMOTLIN28BPAK4CTGFVGLL4NRASHRASPPP1R12AFOXM1PAK1AJUBAPAK2KRASCTNNA1Cytoplasmic retentionLATS2LATS1UbPAKNF2IntegrinNF2MIR98PPP1CAPPP1CBPPP1CCDCAF1CUL4ADDB1RBX1YAP1WWTR1


Description

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.

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Ontology Terms

 

Bibliography

  1. Sekido Y; ''Targeting the Hippo Pathway Is a New Potential Therapeutic Modality for Malignant Mesothelioma.''; Cancers (Basel), 2018 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
128259view00:23, 30 January 2024EweitzStandardize case
127212view19:44, 17 August 2023Khanspersupdated YAP/TAZ and added phosphosites
116745view16:33, 11 May 2021AlexanderPicoReverted to version '04:01, 11 May 2021' by AlexanderPico
116744view16:29, 11 May 2021AlexanderPicoReverted to version '02:44, 1 March 2019' by AlexanderPico
116738view11:01, 11 May 2021EweitzOntology Term : 'DOID:1790' removed !
116737view11:00, 11 May 2021EweitzOntology Term : 'PW:0000003' removed !
116736view11:00, 11 May 2021EweitzOntology Term : 'PW:0001515' removed !
116735view11:00, 11 May 2021EweitzOntology Term : 'PW:0000013' removed !
116734view10:59, 11 May 2021EweitzModified title
103434view09:44, 1 March 2019Marvin M2Connected last unconnected line
103355view00:00, 23 February 2019AlexanderPicoOntology Term : 'signaling pathway' added !
103354view00:00, 23 February 2019AlexanderPicoOntology Term : 'disease pathway' added !
103353view23:59, 22 February 2019AlexanderPicoOntology Term : 'altered Hippo signaling pathway' added !
103352view23:59, 22 February 2019AlexanderPicoOntology Term : 'Hippo signaling pathway' added !
103351view23:59, 22 February 2019AlexanderPicoOntology Term : 'malignant mesothelioma' added !
103350view23:59, 22 February 2019AlexanderPicoModified description
103349view23:51, 22 February 2019AlexanderPicofixed curved line paths
103348view23:48, 22 February 2019AlexanderPicocompleted model
103315view01:15, 22 February 2019AlexanderPicoNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AJUBAGeneProduct84962 (Entrez Gene) AJUBA
AMOTGeneProduct154796 (Entrez Gene) AMOT
CCND1GeneProduct595 (Entrez Gene) CCND1,
CD44GeneProduct960 (Entrez Gene) CD44
CDH10GeneProduct1008 (Entrez Gene) Cadherin
CDH11GeneProduct1009 (Entrez Gene) Cadherin
CDH12GeneProduct1010 (Entrez Gene) Cadherin
CDH13GeneProduct1012 (Entrez Gene) Cadherin
CDH15GeneProduct1013 (Entrez Gene) Cadherin
CDH16GeneProduct1014 (Entrez Gene) Cadherin
CDH17GeneProduct1015 (Entrez Gene) Cadherin
CDH18GeneProduct1016 (Entrez Gene) Cadherin
CDH19GeneProduct28513 (Entrez Gene) Cadherin
CDH1GeneProduct999 (Entrez Gene) Cadherin
CDH20GeneProduct28316 (Entrez Gene) Cadherin
CDH2GeneProduct1000 (Entrez Gene) Cadherin
CDH22GeneProduct64405 (Entrez Gene) Cadherin
CDH24GeneProduct64403 (Entrez Gene) Cadherin
CDH3GeneProduct1001 (Entrez Gene) Cadherin
CDH4GeneProduct1002 (Entrez Gene) Cadherin
CDH5GeneProduct1003 (Entrez Gene) Cadherin
CDH6GeneProduct1004 (Entrez Gene) Cadherin
CDH7GeneProduct1005 (Entrez Gene) Cadherin
CDH8GeneProduct1006 (Entrez Gene) Cadherin
CDH9GeneProduct1007 (Entrez Gene) Cadherin
CSF1RGeneProductENSG00000182578 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:12978
CTGFGeneProduct1490 (Entrez Gene) CTGF
CTNNA1GeneProduct1495 (Entrez Gene) β-cat
CTNNB1GeneProduct1499 (Entrez Gene) β-cat
CUL4AGeneProduct8451 (Entrez Gene) Nf2
CXCL10GeneProduct3627 (Entrez Gene) MOB1
DCAF1GeneProduct9730 (Entrez Gene) Nf2
DDB1GeneProduct1642 (Entrez Gene) Nf2
EGFRGeneProductENSG00000146648 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:13649
EPHA2GeneProductENSG00000142627 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:13836
FGFR1GeneProductENSG00000077782 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14182
FGFR2GeneProductENSG00000066468 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14183
FGFR3GeneProductENSG00000068078 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14184
FGFR4GeneProductENSG00000160867 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14186
FLT1GeneProductENSG00000102755 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14254
FLT3GeneProductENSG00000122025 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14257
FLT4GeneProductENSG00000037280 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14257
FOXM1GeneProduct2305 (Entrez Gene) FOXM1
HRASGeneProduct3265 (Entrez Gene) RAS
IGF1RGeneProductENSG00000140443 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16001
INSRGeneProductENSG00000171105 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16337
ITGA10GeneProductITGA10 (HGNC)
ITGA11GeneProductITGA11 (HGNC)
ITGA1GeneProductITGA1 (HGNC)
ITGA2BGeneProductITGA2B (HGNC)
ITGA2GeneProductITGA2 (HGNC)
ITGA3GeneProductITGA3 (HGNC)
ITGA4GeneProductITGA4 (HGNC)
ITGA5GeneProductITGA5 (HGNC)
ITGA6GeneProductITGA6 (HGNC)
ITGA7GeneProductITGA7 (HGNC)
ITGA8GeneProductITGA8 (HGNC)
ITGA9GeneProductITGA9 (HGNC)
ITGADGeneProductITGAD (HGNC)
ITGAEGeneProductITGAE (HGNC)
ITGALGeneProductITGAL (HGNC)
ITGAMGeneProductITGAM (HGNC)
ITGAVGeneProductITGAV (HGNC)
ITGAXGeneProductITGAX (HGNC)
ITGB1GeneProductITGB1 (HGNC)
ITGB2GeneProductITGB2 (HGNC)
ITGB3GeneProductITGB3 (HGNC)
ITGB4GeneProductITGB4 (HGNC)
ITGB5GeneProductITGB5 (HGNC)
ITGB6GeneProductITGB6 (HGNC)
ITGB7GeneProductITGB7 (HGNC)
ITGB8GeneProductITGB8 (HGNC)
KDRGeneProductENSG00000128052 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16542
KITGeneProductENSG00000157404 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16590
KRASGeneProduct3845 (Entrez Gene) RAS
LATS1GeneProduct9113 (Entrez Gene) LATS1/2
LATS2GeneProduct26524 (Entrez Gene) LATS1/2
LIN28BGeneProduct389421 (Entrez Gene) Lin28B
METGeneProductENSG00000105976 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:17295
MIR98GeneProduct407054 (Entrez Gene) Nf2
MYCGeneProduct4609 (Entrez Gene) MYC
NF2Rna4771 (Entrez Gene) Nf2
NGFRGeneProductENSG00000064300 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18053
NRASGeneProduct4893 (Entrez Gene) RAS
NTRK1GeneProductENSG00000198400 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:21687
NTRK2GeneProductENSG00000148053 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:21687
PAK1GeneProduct5058 (Entrez Gene) PAK,PKAMerlin
PAK2GeneProduct5062 (Entrez Gene) PAK,PKAMerlin
PAK3GeneProduct5063 (Entrez Gene) PAK,PKAMerlin
PAK4GeneProduct10298 (Entrez Gene) PAK,PKAMerlin
PAK5GeneProduct57144 (Entrez Gene) PAK,PKAMerlin
PAK6GeneProduct56924 (Entrez Gene) PAK,PKAMerlin
PDGFRAGeneProductENSG00000134853 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18595
PDGFRBGeneProductENSG00000113721 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18596
PLCB4GeneProduct5332 (Entrez Gene) PLCB4
PPP1CAGeneProduct5499 (Entrez Gene) MYPT-1
PPP1CBGeneProduct5500 (Entrez Gene) MYPT-1
PPP1CCGeneProduct5501 (Entrez Gene) MYPT-1
PPP1R12AGeneProduct4659 (Entrez Gene) MYPT-1
PPP1R14AGeneProduct94274 (Entrez Gene) CPI-17
PRKACAGeneProduct5566 (Entrez Gene) PKA
PRKACBGeneProduct5567 (Entrez Gene) PKA
PRKACGGeneProduct5568 (Entrez Gene) PKA
PRKAR1AGeneProduct5573 (Entrez Gene) PKA
PRKAR1BGeneProduct5575 (Entrez Gene) PKA
PRKAR2AGeneProduct5576 (Entrez Gene) PKA
PRKAR2BGeneProduct5577 (Entrez Gene) PKA
PTK2GeneProduct5747 (Entrez Gene) FAK
RBX1GeneProduct9978 (Entrez Gene) Nf2
SAV1GeneProduct60485 (Entrez Gene) SAV1
STK3GeneProduct6788 (Entrez Gene) MST1/2
STK4GeneProduct4485 (Entrez Gene) MST1/2
TEAD1GeneProductENSG00000187079 (Ensembl)
TEAD2GeneProductENSG00000074219 (Ensembl)
TEAD3GeneProductENSG00000007866 (Ensembl)
TEAD4GeneProductENSG00000197905 (Ensembl)
TEKGeneProductENSG00000120156 (Ensembl) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:21687
VGLL4GeneProduct9686 (Entrez Gene) VGLL4
WWTR1GeneProduct25937 (Entrez Gene) YAP/TAZ
YAP1GeneProduct10413 (Entrez Gene) YAP/TAZ

Annotated Interactions

No annotated interactions

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