A-kinase anchor protein 11

AKAP11 (A-kinase anchor protein 11) is a scaffolding protein that binds to type II regulatory subunits of protein kinase A, anchoring and directing them to specific cellular locations (UniProt: Q9UKA4). At 210 kDa, this large protein functions as a spatial organizer of cAMP-dependent signaling. AKAP11 is expressed in human tissues and participates in compartmentalized protein kinase A signaling, which regulates diverse cellular processes including gene transcription, metabolism, and cytoskeletal dynamics.

In Alzheimer's Disease, AKAP11 is consistently downregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). Quantitative proteomics analysis using TMT labeling across four subcellular fractions (P2, P3, S2, S3) in a DDA experiment revealed a mean log2 fold-change of −0.24, indicating modest but reproducible reduction. This downregulation suggests impaired cAMP signaling organization in AD pathology. Given the scaffolding role of AKAP11 in kinase localization, reduced levels may contribute to dysregulation of phosphorylation-dependent cellular processes implicated in neurodegeneration.