Neurotrophin receptor tyrosine kinases regulated with near-infrared light

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dc.contributor University of Helsinki, Department of Anatomy en
dc.contributor University of Helsinki, Department of Anatomy en
dc.contributor University of Helsinki, Department of Anatomy en
dc.contributor.author Leopold, Anna V.
dc.contributor.author Chernov, Konstantin G.
dc.contributor.author Shemetov, Anton A.
dc.contributor.author Verkhusha, Vladislav V.
dc.date.accessioned 2019-03-26T06:39:01Z
dc.date.available 2019-03-26T06:39:01Z
dc.date.issued 2019-03-08
dc.identifier.citation Leopold , A V , Chernov , K G , Shemetov , A A & Verkhusha , V V 2019 , ' Neurotrophin receptor tyrosine kinases regulated with near-infrared light ' , Nature Communications , vol. 10 , 1129 . https://doi.org/10.1038/s41467-019-08988-3 en
dc.identifier.issn 2041-1723
dc.identifier.other PURE: 123523027
dc.identifier.other PURE UUID: f690521b-d756-4c1a-bba4-996516295bf3
dc.identifier.other WOS: 000460631100014
dc.identifier.other Scopus: 85062617068
dc.identifier.uri http://hdl.handle.net/10138/300394
dc.description.abstract Optical control over the activity of receptor tyrosine kinases (RTKs) provides an efficient way to reversibly and non-invasively map their functions. We combined catalytic domains of Trk (tropomyosin receptor kinase) family of RTKs, naturally activated by neurotrophins, with photosensory core module of DrBphP bacterial phytochrome to develop opto-kinases, termed Dr-TrkA and Dr-TrkB, reversibly switchable on and off with near-infrared and far-red light. We validated Dr-Trk ability to reversibly light-control several RTK pathways, calcium level, and demonstrated that their activation triggers canonical Trk signaling. Dr-TrkA induced apoptosis in neuroblastoma and glioblastoma, but not in other cell types. Absence of spectral crosstalk between Dr-Trks and blue-light-activatable LOV-domain-based translocation system enabled intracellular targeting of Dr-TrkA independently of its activation, additionally modulating Trk signaling. Dr-Trks have several superior characteristics that make them the opto-kinases of choice for regulation of RTK signaling: high activation range, fast and reversible photoswitching, and multiplexing with visible-light-controllable optogenetic tools. en
dc.format.extent 13
dc.language.iso eng
dc.relation.ispartof Nature Communications
dc.rights en
dc.subject CELL-DEATH en
dc.subject FLUORESCENT PROTEINS en
dc.subject TRKA en
dc.subject ACTIVATION en
dc.subject BIOSENSORS en
dc.subject TOOLS en
dc.subject ERK en
dc.subject 3111 Biomedicine en
dc.title Neurotrophin receptor tyrosine kinases regulated with near-infrared light en
dc.type Article
dc.description.version Peer reviewed
dc.identifier.doi https://doi.org/10.1038/s41467-019-08988-3
dc.type.uri info:eu-repo/semantics/other
dc.type.uri info:eu-repo/semantics/publishedVersion
dc.contributor.pbl
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