CDK5:p25 phosphorylates JUN

Stable Identifier
R-HSA-8868666
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
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CDK5:p25 phosphorylates JUN
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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).

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Output
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Catalyst Activity

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

Physical Entity
CDK5:p25 [cytosol] (Homo sapiens)
Activity
protein serine/threonine kinase activity (GO:0004674)
Inferred From
Cdk5:p25 phosphorylates Jun (Mus musculus)
Disease
Name Identifier Synonyms
Alzheimer's disease DOID:10652 AD, Alzheimers dementia, Alzheimer disease
Authored
Shah, K  (2016-02-23)
Created
Orlic-Milacic, M  (2016-04-22)
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