{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gupta R"],"funding":["Evangelisches Studienwerk Villigst","Deutsche Forschungsgemeinschaft","Deutsche Forschungsgemeinschaft (German Research Foundation)","Interdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum Würzburg","Interdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum Würzburg (Interdisciplinary Center for Clinical Research, University Hospital of Würzburg)"],"pagination":["1357-1379"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11405271"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["31(9)"],"pubmed_abstract":["Trk (NTRK) receptor and NTRK gene fusions are oncogenic drivers of a wide variety of tumors. Although Trk receptors are typically activated at the cell surface, signaling of constitutive active Trk and diverse intracellular NTRK fusion oncogenes is barely investigated. Here, we show that a high intracellular abundance is sufficient for neurotrophin-independent, constitutive activation of TrkB kinase domains. In HEK293 cells, constitutive active TrkB kinase and an intracellular NTRK2-fusion oncogene (SQSTM1-NTRK2) reduced actin filopodia dynamics, phosphorylated FAK, and altered the cell morphology. Atypical cellular responses could be mimicked with the intracellular kinase domain, which did not activate the Trk-associated MAPK/ERK pathway. In glioblastoma-like U87MG cells, expression of Tr"],"journal":["Cancer gene therapy"],"pubmed_title":["Atypical cellular responses mediated by intracellular constitutive active TrkB (NTRK2) kinase domains and a solely intracellular NTRK2-fusion oncogene."],"pmcid":["PMC11405271"],"funding_grant_id":["project ID: 326998133; CRC TRR225 (B01)","B-450","project-ID: 194101929 (BL567/3-2)","project Z-6"],"pubmed_authors":["Gupta R","Villmann C","Horn E","Dittmeier M","Nickl V","Kuper J","Langlhofer G","Monoranu CM","Sodmann A","Wegat V","Wachter B","Havlicek S","Luzak V","Wohlleben G","Bischler T","Doll D","Gupta J","Luningschror P","Blum R","Wischhusen J","Polat B","Bady E"],"additional_accession":[]},"is_claimable":false,"name":"Atypical cellular responses mediated by intracellular constitutive active TrkB (NTRK2) kinase domains and a solely intracellular NTRK2-fusion oncogene.","description":"Trk (NTRK) receptor and NTRK gene fusions are oncogenic drivers of a wide variety of tumors. Although Trk receptors are typically activated at the cell surface, signaling of constitutive active Trk and diverse intracellular NTRK fusion oncogenes is barely investigated. Here, we show that a high intracellular abundance is sufficient for neurotrophin-independent, constitutive activation of TrkB kinase domains. In HEK293 cells, constitutive active TrkB kinase and an intracellular NTRK2-fusion oncogene (SQSTM1-NTRK2) reduced actin filopodia dynamics, phosphorylated FAK, and altered the cell morphology. Atypical cellular responses could be mimicked with the intracellular kinase domain, which did not activate the Trk-associated MAPK/ERK pathway. In glioblastoma-like U87MG cells, expression of Tr","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Sep","modification":"2026-07-15T09:35:28.894Z","creation":"2025-04-04T08:22:26.566Z"},"accession":"S-EPMC11405271","cross_references":{"pubmed":["39039193"],"doi":["10.1038/s41417-024-00809-0"]}}