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Impaired dynamin 2 function leads to increased AP-1 transcriptional activity through the JNK/c-Jun pathway
- Source :
- Cellular Signalling. 28(1):160-171
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Activation of AP-1 transcription factors, composed of the Jun and Fos proteins, regulates cellular fates, such as proliferation, differentiation or apoptosis. Among other stimuli, the AP-1 pathway can be initiated by extracellular ligands, such as growth factors or cytokines, which undergo internalization in complex with their receptors. Endocytosis has been implicated in the regulation of several signaling pathways; however its possible impact on AP-1 signaling remains unknown. Here we show that inhibition of dynamin 2 (Dyn2), a major regulator of endocytic internalization, strongly stimulates the AP-1 pathway. Specifically, expression of a dominant-negative Dyn2 K44A mutant increases the total levels of c-Jun, its phosphorylation on Ser63/73 and transcription of AP-1 target genes. Interestingly, DNM2 mutations implicated in human neurological disorders exhibit similar effects on AP-1 signaling. Mechanistically, Dyn2 K44A induces AP-1 by increasing phosphorylation of several receptor tyrosine kinases. Their activation is required to initiate a Src- and JNK-dependent signaling cascade converging on c-Jun and stimulating expression of AP-1 target genes. Cumulatively, our data uncover a link between the Dyn2 function and JNK signaling which leads to AP-1 induction.
- Subjects :
- 0301 basic medicine
Transcriptional Activation
MAP Kinase Signaling System
Proto-Oncogene Proteins c-jun
media_common.quotation_subject
Receptor tyrosine kinase
03 medical and health sciences
Dynamin II
Receptor tyrosine kinases
Humans
Phosphorylation
Internalization
Transcription factor
Cells, Cultured
media_common
Dynamin
biology
c-Jun
c-jun
JNK Mitogen-Activated Protein Kinases
JAK-STAT signaling pathway
Cell Biology
AP-1
Cell biology
Transcription Factor AP-1
030104 developmental biology
biology.protein
Cancer research
Signal transduction
Subjects
Details
- ISSN :
- 08986568
- Volume :
- 28
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Cellular Signalling
- Accession number :
- edsair.doi.dedup.....af0cba27047d3548aca406a2466a4fbc
- Full Text :
- https://doi.org/10.1016/j.cellsig.2015.10.002