Arndt-Jovin, Donna J.

[["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.volume","108"],["dc.contributor.author","Valley, Christopher C."],["dc.contributor.author","Arndt-Jovin, Donna J."],["dc.contributor.author","Jovin, Thomas M."],["dc.contributor.author","Steinkamp, Mara P."],["dc.contributor.author","Chizhik, Alexey I."],["dc.contributor.author","Karedla, Narain V. R."],["dc.contributor.author","Hlavacek, William S."],["dc.contributor.author","Wilson, Bridget S."],["dc.contributor.author","Lidke, Keith A."],["dc.contributor.author","Lidke, Diane S."],["dc.date.accessioned","2018-11-07T10:01:57Z"],["dc.date.available","2018-11-07T10:01:57Z"],["dc.date.issued","2015"],["dc.format.extent","351A"],["dc.identifier.isi","000362849400177"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/38135"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Cell Press"],["dc.publisher.place","Cambridge"],["dc.relation.conference","59th Annual Meeting of the Biophysical-Society"],["dc.relation.eventlocation","Baltimore, MD"],["dc.relation.issn","1542-0086"],["dc.relation.issn","0006-3495"],["dc.title","Inside-Out Signaling of Oncogenic EGFR Mutants Promotes Ligand-Independent Dimerization"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4087"],["dc.bibliographiccitation.issue","22"],["dc.bibliographiccitation.journal","Molecular Biology of the Cell"],["dc.bibliographiccitation.lastpage","4099"],["dc.bibliographiccitation.volume","26"],["dc.contributor.author","Valley, Christopher C."],["dc.contributor.author","Arndt-Jovin, Donna J."],["dc.contributor.author","Karedla, Narain V. R."],["dc.contributor.author","Steinkamp, Mara P."],["dc.contributor.author","Chizhik, Alexey I."],["dc.contributor.author","Hlavacek, William S."],["dc.contributor.author","Wilson, Bridget S."],["dc.contributor.author","Lidke, Keith A."],["dc.contributor.author","Lidke, Diane S."],["dc.date.accessioned","2018-11-07T09:49:02Z"],["dc.date.available","2018-11-07T09:49:02Z"],["dc.date.issued","2015"],["dc.description.abstract","Mutations within the epidermal growth factor receptor (EGFR/erbB1/Her1) are often associated with tumorigenesis. In particular, a number of EGFR mutants that demonstrate ligand-independent signaling are common in non-small cell lung cancer (NSCLC), including kinase domain mutations L858R (also called L834R) and exon 19 deletions (e.g., Delta L747-P753insS), which collectively make up nearly 90% of mutations in NSCLC. The molecular mechanisms by which these mutations confer constitutive activity remain unresolved. Using multiple subdiffraction-limit imaging modalities, we reveal the altered receptor structure and interaction kinetics of NSCLC-associated EGFR mutants. We applied two-color single quantum dot tracking to quantify receptor dimerization kinetics on living cells and show that, in contrast to wild-type EGFR, mutants are capable of forming stable, ligand-independent dimers. Two-color superresolution localization microscopy confirmed ligand-independent aggregation of EGFR mutants. Live-cell Forster resonance energy transfer measurements revealed that the L858R kinase mutation alters ectodomain structure such that unliganded mutant EGFR adopts an extended, dimerization-competent conformation. Finally, mutation of the putative dimerization arm confirmed a critical role for ectodomain engagement in ligand-independent signaling. These data support a model in which dysregulated activity of NSCLC-associated kinase mutants is driven by coordinated interactions involving both the kinase and extracellular domains that lead to enhanced dimerization."],["dc.identifier.doi","10.1091/mbc.E15-05-0269"],["dc.identifier.isi","000366324900022"],["dc.identifier.pmid","26337388"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35430"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Cell Biology"],["dc.relation.issn","1939-4586"],["dc.relation.issn","1059-1524"],["dc.title","Enhanced dimerization drives ligand-independent activity of mutant epidermal growth factor receptor in lung cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.volume","106"],["dc.contributor.author","Arndt-Jovin, Donna J."],["dc.contributor.author","Lidke, Diane S."],["dc.contributor.author","Chizhik, Alexey I."],["dc.contributor.author","Karedla, Narain V. R."],["dc.contributor.author","Jovin, Thomas M."],["dc.date.accessioned","2018-11-07T09:44:57Z"],["dc.date.available","2018-11-07T09:44:57Z"],["dc.date.issued","2014"],["dc.format.extent","237A"],["dc.identifier.isi","000337000401317"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34509"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Cell Press"],["dc.publisher.place","Cambridge"],["dc.relation.conference","58th Annual Meeting of the Biophysical-Society"],["dc.relation.eventlocation","San Francisco, CA"],["dc.relation.issn","1542-0086"],["dc.relation.issn","0006-3495"],["dc.title","Flim-FRET, a Structural Tool for ErbB Receptor Studies in the Living Cell"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]