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.e3cCadherinCadherinCadherinCadherinCadherinCadherinCadherinCadherinCadherinCadherinCadherinCadherinCadherinCadherinCadherinCadherinCadherinCadherinCadherinCadherinCadherinPKAPKAPKAPKAPKAPKAPKALATS1/2MST1/2LATS1/2Nf2MST1/2YAP/TAZYAP/TAZHomology Mapping from Mus musculus to Homo sapiens: Original ID = L:14183Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16542Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16337Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14184Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16001Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16590Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14182Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:13836Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:13649Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:12978Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14186Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14254Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14257Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18053Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:17295Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18595Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18596Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:21687Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14257Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:21687Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:21687MOB1CD44PAK,PKAMerlinSAV1PAK,PKAMerlinPAK,PKAMerlinCPI-17β-catCCND1,MYCFAKPLCB4AMOTLin28BPAK,PKAMerlinCTGFVGLL4RASRASMYPT-1FOXM1PAK,PKAMerlinAJUBAPAK,PKAMerlinRASβ-catLATS1/2LATS1/2Nf2Nf2Nf2MYPT-1MYPT-1MYPT-1Nf2Nf2Nf2Nf2YAP/TAZYAP/TAZparentid=Q9NRM7; parentsymbol=LATS2; site=EHAFyEFtFRRFFDD; position=thr1041;
sitegrpid=31843001; ptm=p; direction=uparentid=O95835; parentsymbol=LATS1; site=EHAFyEFtFRRFFDD; position=thr1079;
sitegrpid=457595; ptm=p; direction=uparentid=P35240; parentsymbol=NF2; site=DTDMKRLsMEIEKEK; position=ser518;
sitegrpid=448282; ptm=p; direction=uparentid=Q13043; parentsymbol=STK4; site=DtMAkRNtVIGTPFW; position=thr183;
sitegrpid=447925; ptm=p; direction=uparentid=P46937; parentsymbol=YAP1; site=ktANVPQtVPMRLRk; position=thr83;
sitegrpid=27460703; ptm=p; direction=dparentid=P46937; parentsymbol=YAP1; site=sGLsMsSySVPRtPD; position=tyr407;
sitegrpid=473004; ptm=p; direction=dparentid=P46937; parentsymbol=YAP1; site=PQHVRAHssPAsLQL; position=ser127;
sitegrpid=448847; ptm=p; direction=dparentid=Q9GZV5; parentsymbol=WWTR1; site=AQHVRsHssPAsLQL; position=ser89;
sitegrpid=457660; ptm=p; direction=d29565815PubMedTargeting the Hippo Pathway Is a New Potential Therapeutic Modality for Malignant Mesothelioma.2018Cancers (Basel)Sekido YHippo signaling pathwayPW:0001515Pathway Ontologydisease pathwayPW:0000013Pathway Ontologyaltered Hippo signaling pathwayPW:0001517Pathway Ontologysignaling pathwayPW:0000003Pathway Ontology