FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3175240802> ?p ?o ?g. }

• W3175240802 abstract "DLK is a master regulator of axonal retraction and regeneration following neuronal injury and contributes to neurodegeneration in numerous animal models of disease, but the mechanisms by which DLK's pro-degenerative actions are constrained in healthy neurons are not known. Data to this point demonstrates that DLK is constitutively expressed in post-mitotic neurons where it is maintained in an inactive state. Once injury occurs, DLK protein is stabilized, phosphorylated, and liberated from inhibitory factors, allowing it to engage the mitogen-activated protein kinase kinase 4 (MKK4) to phospho-c-Jun N-terminal Kinase (JNK) signaling cascade to regulate apoptosis via phospho-c-jun (p-c-jun) and the integrated stress response (ISR) pathway via protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK). Here we report that DLK also functions in healthy neurons as it is constitutively active in the adult mouse cerebellum in the absence of injury. Mouse cerebellar granule cells express full-length DLK protein predominantly in the axon terminals and post-synaptic densities along with abundant nuclear p-c-jun. Pharmacological inhibition of DLK rapidly eliminates nearly all phospho-Mkk4 and nuclear p-c-Jun within 2 hours, demonstrating that c-jun phosphorylation is DLK dependent. To understand how DLK pathway activation differs between homeostatic signaling and disease response, we used western blotting and immunofluorescence to compare the DLK pathway between cerebellum, cortex, and hippocampus in rTg4510 mice, which express human P301L mutant tau in the forebrain where it leads to profound DLK activation and neurodegeneration, with non-transgenic controls. p-c-jun is significantly higher in cerebellum and in the transgenic forebrain areas than in the non-transgenic control forebrain confirming that it is constitutively expressed in the cerebellum and induced from lower basal levels by pathological tau. We next examined the PERK pathway, including phospho-PERK, phospho-eIF2a, and the induction of GADD34, ATF4, and CHOP. Like p-c-jun, PERK signaling was induced in the rTg4510 forebrain, but was not activated to the same extent in the cerebellum, suggesting that DLK signaling during disease involves enhanced PERK signaling. DLK to JNK signaling is orchestrated by the JNK interacting protein (JIP) scaffolding molecules, of which there are 3 members. In contrast to the forebrain, the cerebellum expresses very little JIP3, whereas JIP1 and JIP2 appear similar across regions. Therefore we hypothesize that JIP3 is required for the injury- and disease-induced DLK signaling pathway. Transcriptomics are currently being utilized to elucidate the physiological relevance of constitutive DLK signaling in the cerebellum. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal." @default.
• W3175240802 created "2021-07-05" @default.
• W3175240802 creator A5007972878 @default.
• W3175240802 creator A5009669991 @default.
• W3175240802 creator A5016100832 @default.
• W3175240802 creator A5025901197 @default.
• W3175240802 creator A5054323373 @default.
• W3175240802 creator A5064619094 @default.
• W3175240802 creator A5067485402 @default.
• W3175240802 creator A5068687236 @default.
• W3175240802 creator A5068873272 @default.
• W3175240802 creator A5075934899 @default.
• W3175240802 creator A5091744453 @default.
• W3175240802 date "2018-04-01" @default.
• W3175240802 modified "2023-10-16" @default.
• W3175240802 title "Dual Leucine Zipper Kinase (DLK) Constitutively Signals in the Uninjured Mouse Cerebellum" @default.
• W3175240802 doi "https://doi.org/10.1096/fasebj.2018.32.1_supplement.687.11" @default.
• W3175240802 hasPublicationYear "2018" @default.
• W3175240802 type Work @default.
• W3175240802 sameAs 3175240802 @default.
• W3175240802 citedByCount "0" @default.
• W3175240802 crossrefType "journal-article" @default.
• W3175240802 hasAuthorship W3175240802A5007972878 @default.
• W3175240802 hasAuthorship W3175240802A5009669991 @default.
• W3175240802 hasAuthorship W3175240802A5016100832 @default.
• W3175240802 hasAuthorship W3175240802A5025901197 @default.
• W3175240802 hasAuthorship W3175240802A5054323373 @default.
• W3175240802 hasAuthorship W3175240802A5064619094 @default.
• W3175240802 hasAuthorship W3175240802A5067485402 @default.
• W3175240802 hasAuthorship W3175240802A5068687236 @default.
• W3175240802 hasAuthorship W3175240802A5068873272 @default.
• W3175240802 hasAuthorship W3175240802A5075934899 @default.
• W3175240802 hasAuthorship W3175240802A5091744453 @default.
• W3175240802 hasConcept C121738310 @default.
• W3175240802 hasConcept C124160383 @default.
• W3175240802 hasConcept C126322002 @default.
• W3175240802 hasConcept C137361374 @default.
• W3175240802 hasConcept C169760540 @default.
• W3175240802 hasConcept C184235292 @default.
• W3175240802 hasConcept C2776925932 @default.
• W3175240802 hasConcept C2779134260 @default.
• W3175240802 hasConcept C2779652256 @default.
• W3175240802 hasConcept C2779715522 @default.
• W3175240802 hasConcept C2780723820 @default.
• W3175240802 hasConcept C49805395 @default.
• W3175240802 hasConcept C529278444 @default.
• W3175240802 hasConcept C71924100 @default.
• W3175240802 hasConcept C86803240 @default.
• W3175240802 hasConcept C90934575 @default.
• W3175240802 hasConcept C95444343 @default.
• W3175240802 hasConcept C97029542 @default.
• W3175240802 hasConceptScore W3175240802C121738310 @default.
• W3175240802 hasConceptScore W3175240802C124160383 @default.
• W3175240802 hasConceptScore W3175240802C126322002 @default.
• W3175240802 hasConceptScore W3175240802C137361374 @default.
• W3175240802 hasConceptScore W3175240802C169760540 @default.
• W3175240802 hasConceptScore W3175240802C184235292 @default.
• W3175240802 hasConceptScore W3175240802C2776925932 @default.
• W3175240802 hasConceptScore W3175240802C2779134260 @default.
• W3175240802 hasConceptScore W3175240802C2779652256 @default.
• W3175240802 hasConceptScore W3175240802C2779715522 @default.
• W3175240802 hasConceptScore W3175240802C2780723820 @default.
• W3175240802 hasConceptScore W3175240802C49805395 @default.
• W3175240802 hasConceptScore W3175240802C529278444 @default.
• W3175240802 hasConceptScore W3175240802C71924100 @default.
• W3175240802 hasConceptScore W3175240802C86803240 @default.
• W3175240802 hasConceptScore W3175240802C90934575 @default.
• W3175240802 hasConceptScore W3175240802C95444343 @default.
• W3175240802 hasConceptScore W3175240802C97029542 @default.
• W3175240802 hasIssue "S1" @default.
• W3175240802 hasLocation W31752408021 @default.
• W3175240802 hasOpenAccess W3175240802 @default.
• W3175240802 hasPrimaryLocation W31752408021 @default.
• W3175240802 hasRelatedWork W1560294775 @default.
• W3175240802 hasRelatedWork W1964392751 @default.
• W3175240802 hasRelatedWork W1972151119 @default.
• W3175240802 hasRelatedWork W2005969483 @default.
• W3175240802 hasRelatedWork W2017854403 @default.
• W3175240802 hasRelatedWork W2038244362 @default.
• W3175240802 hasRelatedWork W2079712059 @default.
• W3175240802 hasRelatedWork W2160227323 @default.
• W3175240802 hasRelatedWork W3008609042 @default.
• W3175240802 hasRelatedWork W3175240802 @default.
• W3175240802 hasVolume "32" @default.
• W3175240802 isParatext "false" @default.
• W3175240802 isRetracted "false" @default.
• W3175240802 magId "3175240802" @default.
• W3175240802 workType "article" @default.