Protein kinase A (PKA) signaling pathway (PKA pathway)

The Protein kinase A (PKA) signaling pathway is a fundamental intracellular cascade that regulates diverse cellular processes, including metabolism, gene expression, and cell growth (StatPearls, 2023). It is primarily triggered by the activation of G protein-coupled receptors (GPCRs), which stimulate adenylyl cyclase to produce the second messenger cyclic AMP (cAMP) (UniProt, 2024). cAMP binds to the regulatory subunits of the PKA tetramer, inducing a conformational change that releases active catalytic subunits to phosphorylate target proteins such as the cAMP response element-binding protein (CREB) (PubMed, 2022). This pathway is essential for physiological functions like cardiac contractility and glucose homeostasis, but its dysregulation is linked to diseases such as Cushing's syndrome, Carney complex, and various cancers (NIH, 2023). Therapeutic strategies often target components of this pathway, such as phosphodiesterases (PDEs) to modulate cAMP levels or direct PKA inhibitors, though the pathway's ubiquitous nature poses significant risks for off-target effects and systemic toxicity (Nature Reviews Drug Discovery, 2021).

Other names

cAMP-dependent protein kinase pathwaycAMP/PKA signaling pathwayProtein kinase A pathway

The pathway is activated when ligands bind to Gs-coupled receptors, stimulating adenylyl cyclase to convert ATP into cAMP. cAMP then binds to the regulatory subunits of PKA, causing the release of active catalytic subunits that phosphorylate serine/threonine residues on downstream effectors (StatPearls, 2023).