cAMP-dependent protein kinase catalytic subunit alpha

Summary

PRKACA (cAMP-dependent protein kinase catalytic subunit alpha, or PKA C-alpha) is a ubiquitous serine/threonine kinase that phosphorylates numerous substrates in cytoplasmic and nuclear compartments (UniProt: P17612). It regulates diverse cellular processes including signal transduction, gene expression, platelet function, and meiotic control through phosphorylation of targets such as NFKB1, CLDN3, RYR2, and HSF1. The protein is also implicated in Hedgehog signaling inhibition and ciliogenesis during embryonic development.

PRKACA is associated with adrenocortical and cardiac developmental disorders; mutations cause primary pigmented nodular adrenocortical disease and cardioacrofacial dysplasia (UniProt: P17612). The protein's broad signaling capacity suggests involvement in multiple tissue contexts, though specific pathway enrichment in any single tissue is not detailed in the available record.

In Alzheimer's disease, PRKACA shows ambiguous direction of change across subcellular fractions from post-mortem AD brain proteomics, with a mean log2 fold-change of −0.12 relative to age-matched controls (Chaparral AD proteomics). This modest, inconsistent signal across fractions suggests either minimal overall dysregulation or compartment-specific changes that warrant further investigation in AD pathology.