Reactome: A Curated Pathway Database

CDK5:p25 phosphorylates JUN

Stable Identifier
R-HSA-8868666
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

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
Participant Of
This entity is regulated by:
Title Physical Entity Activity
protein serine/threonine kinase activity of CDK5:p25 [cytosol] CDK5:p25 [cytosol] protein serine/threonine kinase activity (0004674)
Inferred From
Disease
Diseases
Name Identifier Synonyms
Alzheimer's disease 10652 AD, Alzheimers dementia, Alzheimer disease