General Information:

Id: 7,250 (click here to show other Interactions for entry)
Diseases: Alzheimer disease - [OMIM]
Homo sapiens
HEK293 cells; ES-cell-derived human neurons
Reference: Huang YA et al.(2017) ApoE2, ApoE3, and ApoE4 Differentially Stimulate APP Transcription and Abeta Secretion Cell 168: 427-441.e21 [PMID: 28111074]

Interaction Information:

Comment The three human ApoE isoforms increased DLK levels with the same differential potency as for the stimulation of Abeta synthesis and ERK1/2 phosphorylation (ApoE4>ApoE3>ApoE2). ApoE binding to ApoE receptors activates dual leucine-zipper kinase (DLK), a MAP-kinase kinase kinase that then activates MKK7 and ERK1/2 MAP kinases. Activated ERK1/2 induces cFos phosphorylation, stimulating the transcription factor AP-1, which in turn enhances transcription of amyloid-beta precursor protein (APP) and thereby increases amyloid-beta levels. This molecular mechanism also regulates APP transcription in mice in vivo.
Formal Description
Interaction-ID: 71334

gene/protein mutant

APOE (isoform E4)

increases_activity of



in human neurons; compared to ApoE3 and ApoE2; via binding to ApoE receptors