FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3042108742> ?p ?o ?g. }

• W3042108742 endingPage "4849" @default.
• W3042108742 startingPage "4849" @default.
• W3042108742 abstract "Dual leucine zipper kinase (DLK, Map3k12) is an axonal protein that governs the balance between degeneration and regeneration through its downstream effectors c-jun N-terminal kinase (JNK) and phosphorylated c-jun (p-c-Jun). In peripheral nerves DLK is generally inactive until induced by injury, after which it transmits signals to the nucleus via retrograde transport. Here we report that in contrast to this mode of regulation, in the uninjured adult mouse cerebellum, DLK constitutively drives nuclear p-c-Jun in cerebellar granule neurons, whereas in the forebrain, DLK is similarly expressed and active, but nuclear p-c-Jun is undetectable. When neurodegeneration results from mutant human tau in the rTg4510 mouse model, p-c-Jun then accumulates in neuronal nuclei in a DLK-dependent manner, and the extent of p-c-Jun correlates with markers of synaptic loss and gliosis. This regional difference in DLK-dependent nuclear p-c-Jun accumulation could relate to differing levels of JNK scaffolding proteins, as the cerebellum preferentially expresses JNK-interacting protein-1 (JIP-1), whereas the forebrain contains more JIP-3 and plenty of SH3 (POSH). To characterize the functional differences between constitutive- versus injury-induced DLK signaling, RNA sequencing was performed after DLK inhibition in the cerebellum and in the non-transgenic and rTg4510 forebrain. In all contexts, DLK inhibition reduced a core set of transcripts that are associated with the JNK pathway. Non-transgenic forebrain showed almost no other transcriptional changes in response to DLK inhibition, whereas the rTg4510 forebrain and the cerebellum exhibited distinct differentially expressed gene signatures. In the cerebellum, but not the rTg4510 forebrain, pathway analysis indicated that DLK regulates insulin growth factor-1 (IGF1) signaling through the transcriptional induction of IGF1 binding protein-5 (IGFBP5), which was confirmed and found to be functionally relevant by measuring signaling through the IGF1 receptor. Together these data illuminate the complex multi-functional nature of DLK signaling in the central nervous system (CNS) and demonstrate its role in homeostasis as well as tau-mediated neurodegeneration." @default.
• W3042108742 created "2020-07-16" @default.
• W3042108742 creator A5006058814 @default.
• W3042108742 creator A5009669991 @default.
• W3042108742 creator A5020212737 @default.
• W3042108742 creator A5023312825 @default.
• W3042108742 creator A5024446376 @default.
• W3042108742 creator A5025901197 @default.
• W3042108742 creator A5037970773 @default.
• W3042108742 creator A5054323373 @default.
• W3042108742 creator A5064619094 @default.
• W3042108742 creator A5067485402 @default.
• W3042108742 creator A5068687236 @default.
• W3042108742 creator A5068873272 @default.
• W3042108742 creator A5091744453 @default.
• W3042108742 date "2020-07-09" @default.
• W3042108742 modified "2023-10-16" @default.
• W3042108742 title "Dual Leucine Zipper Kinase Is Constitutively Active in the Adult Mouse Brain and Has Both Stress-Induced and Homeostatic Functions" @default.
• W3042108742 cites W1535972616 @default.
• W3042108742 cites W1963716059 @default.
• W3042108742 cites W1968195620 @default.
• W3042108742 cites W1983506606 @default.
• W3042108742 cites W1990418954 @default.
• W3042108742 cites W1999485246 @default.
• W3042108742 cites W2002143632 @default.
• W3042108742 cites W2004126223 @default.
• W3042108742 cites W2010289572 @default.
• W3042108742 cites W2011760895 @default.
• W3042108742 cites W2013500926 @default.
• W3042108742 cites W2017688356 @default.
• W3042108742 cites W2022746305 @default.
• W3042108742 cites W2022903577 @default.
• W3042108742 cites W2029630756 @default.
• W3042108742 cites W2034247990 @default.
• W3042108742 cites W2036662476 @default.
• W3042108742 cites W2042776153 @default.
• W3042108742 cites W2043576437 @default.
• W3042108742 cites W2045214083 @default.
• W3042108742 cites W2046071339 @default.
• W3042108742 cites W2046141144 @default.
• W3042108742 cites W2049474406 @default.
• W3042108742 cites W2053504155 @default.
• W3042108742 cites W2056415191 @default.
• W3042108742 cites W2068539809 @default.
• W3042108742 cites W2070270733 @default.
• W3042108742 cites W2074463881 @default.
• W3042108742 cites W2085701634 @default.
• W3042108742 cites W2088062973 @default.
• W3042108742 cites W2101704246 @default.
• W3042108742 cites W2108234281 @default.
• W3042108742 cites W2110520657 @default.
• W3042108742 cites W2114638395 @default.
• W3042108742 cites W2119009867 @default.
• W3042108742 cites W2121955382 @default.
• W3042108742 cites W2133711843 @default.
• W3042108742 cites W2134526812 @default.
• W3042108742 cites W2135309154 @default.
• W3042108742 cites W2137579141 @default.
• W3042108742 cites W2149745285 @default.
• W3042108742 cites W2160021202 @default.
• W3042108742 cites W2169456326 @default.
• W3042108742 cites W2172045582 @default.
• W3042108742 cites W2172121366 @default.
• W3042108742 cites W2217207757 @default.
• W3042108742 cites W2293311540 @default.
• W3042108742 cites W2408483783 @default.
• W3042108742 cites W2576070094 @default.
• W3042108742 cites W2747341145 @default.
• W3042108742 cites W2755246776 @default.
• W3042108742 cites W2756048632 @default.
• W3042108742 cites W2762820448 @default.
• W3042108742 cites W2775546495 @default.
• W3042108742 cites W4232737588 @default.
• W3042108742 doi "https://doi.org/10.3390/ijms21144849" @default.
• W3042108742 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7402291" @default.
• W3042108742 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32659913" @default.
• W3042108742 hasPublicationYear "2020" @default.
• W3042108742 type Work @default.
• W3042108742 sameAs 3042108742 @default.
• W3042108742 citedByCount "7" @default.
• W3042108742 countsByYear W30421087422020 @default.
• W3042108742 countsByYear W30421087422021 @default.
• W3042108742 countsByYear W30421087422022 @default.
• W3042108742 countsByYear W30421087422023 @default.
• W3042108742 crossrefType "journal-article" @default.
• W3042108742 hasAuthorship W3042108742A5006058814 @default.
• W3042108742 hasAuthorship W3042108742A5009669991 @default.
• W3042108742 hasAuthorship W3042108742A5020212737 @default.
• W3042108742 hasAuthorship W3042108742A5023312825 @default.
• W3042108742 hasAuthorship W3042108742A5024446376 @default.
• W3042108742 hasAuthorship W3042108742A5025901197 @default.
• W3042108742 hasAuthorship W3042108742A5037970773 @default.
• W3042108742 hasAuthorship W3042108742A5054323373 @default.
• W3042108742 hasAuthorship W3042108742A5064619094 @default.
• W3042108742 hasAuthorship W3042108742A5067485402 @default.
• W3042108742 hasAuthorship W3042108742A5068687236 @default.
• W3042108742 hasAuthorship W3042108742A5068873272 @default.
• W3042108742 hasAuthorship W3042108742A5091744453 @default.

• next