CDK5:p25 phosphorylates JUN

Stable Identifier
R-HSA-8868666
Type
Reaction [transition]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
Based on mouse model studies, the JUN transcription factor undergoes biphasic activation in Alzheimer's disease. JUN is phosphorylated directly by p25-bound CDK5 at serine residues S63 and S73. CDK5:p25-mediated increase in the level of reactive oxygen species (ROS) triggers activation of JNK kinases (MAPK8, MAPK9, MAPK10), which phosphorylate JUN at S63 and S73 at a later time point (Sun et al. 2009).

Aberrant activation of CDK5 by p25 binding also triggers activation of MKK6 (MAP2K6), a p38 MAP kinase. Levels of phosphorylated MAP2K6 are increased in Alzheimer's disease. Activation of p38 MAP kinase(s) results in increased JUN expression (Chang et al. 2010).

Participants
Participates
Catalyst Activity

protein serine/threonine kinase activity of CDK5:p25 [cytosol]

Inferred From
Disease
Name Identifier Synonyms
Alzheimer's disease DOID:10652 AD, Alzheimers dementia, Alzheimer disease
Authored
Created
Cite Us!