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. e3c Cadherin Cadherin Cadherin Cadherin Cadherin Cadherin Cadherin Cadherin Cadherin Cadherin Cadherin Cadherin Cadherin Cadherin Cadherin Cadherin Cadherin Cadherin Cadherin Cadherin Cadherin PKA PKA PKA PKA PKA PKA PKA LATS1/2 MST1/2 LATS1/2 Nf2 MST1/2 YAP/TAZ YAP/TAZ Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14183 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16542 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16337 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14184 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16001 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16590 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14182 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:13836 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:13649 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:12978 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14186 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14254 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14257 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18053 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:17295 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18595 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18596 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:21687 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14257 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:21687 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:21687 MOB1 CD44 PAK,PKAMerlin SAV1 PAK,PKAMerlin PAK,PKAMerlin CPI-17 β-cat CCND1, MYC FAK PLCB4 AMOT Lin28B PAK,PKAMerlin CTGF VGLL4 RAS RAS MYPT-1 FOXM1 PAK,PKAMerlin AJUBA PAK,PKAMerlin RAS β-cat LATS1/2 LATS1/2 Nf2 Nf2 Nf2 MYPT-1 MYPT-1 MYPT-1 Nf2 Nf2 Nf2 Nf2 YAP/TAZ YAP/TAZ parentid=Q9NRM7; parentsymbol=LATS2; site=EHAFyEFtFRRFFDD; position=thr1041; sitegrpid=31843001; ptm=p; direction=u parentid=O95835; parentsymbol=LATS1; site=EHAFyEFtFRRFFDD; position=thr1079; sitegrpid=457595; ptm=p; direction=u parentid=P35240; parentsymbol=NF2; site=DTDMKRLsMEIEKEK; position=ser518; sitegrpid=448282; ptm=p; direction=u parentid=Q13043; parentsymbol=STK4; site=DtMAkRNtVIGTPFW; position=thr183; sitegrpid=447925; ptm=p; direction=u parentid=P46937; parentsymbol=YAP1; site=ktANVPQtVPMRLRk; position=thr83; sitegrpid=27460703; ptm=p; direction=d parentid=P46937; parentsymbol=YAP1; site=sGLsMsSySVPRtPD; position=tyr407; sitegrpid=473004; ptm=p; direction=d parentid=P46937; parentsymbol=YAP1; site=PQHVRAHssPAsLQL; position=ser127; sitegrpid=448847; ptm=p; direction=d parentid=Q9GZV5; parentsymbol=WWTR1; site=AQHVRsHssPAsLQL; position=ser89; sitegrpid=457660; ptm=p; direction=d 29565815 PubMed Targeting the Hippo Pathway Is a New Potential Therapeutic Modality for Malignant Mesothelioma. 2018 Cancers (Basel) Sekido Y Hippo signaling pathway PW:0001515 Pathway Ontology disease pathway PW:0000013 Pathway Ontology altered Hippo signaling pathway PW:0001517 Pathway Ontology signaling pathway PW:0000003 Pathway Ontology