cAMP-dependent protein kinase (Protein Kinase A) (PKA)

cAMP-dependent protein kinase (PKA) is a ubiquitous serine/threonine kinase that serves as the primary effector of the second messenger cyclic AMP (cAMP) in eukaryotic cells (StatPearls, 2023). The enzyme typically exists as a heterotetrameric holoenzyme composed of two regulatory subunits and two catalytic subunits; upon the binding of cAMP to the regulatory subunits, the catalytic subunits dissociate and become active (UniProt, 2024). These active subunits subsequently phosphorylate a wide array of cytoplasmic and nuclear targets, such as the cAMP-response element-binding (CREB) protein, thereby regulating diverse physiological processes including metabolism, cell growth, and synaptic plasticity (PubMed: 10648231). Dysregulation of PKA signaling is implicated in various pathologies, including Carney complex, Cushing's syndrome, and several types of cancer (NIH, 2022). Because PKA is involved in many essential cellular functions, therapeutic strategies often focus on indirect modulation via G protein-coupled receptors or phosphodiesterases to achieve tissue-specific effects and minimize systemic toxicity (PubMed: 28814723).

Other names

Protein Kinase AAdenosine 3',5'-monophosphate-dependent protein kinasePKA signaling pathwaycAMP-PKA pathway

PKA is activated by the binding of cAMP to its regulatory subunits, which induces a conformational change that releases active catalytic subunits to phosphorylate serine and threonine residues on specific substrate proteins (StatPearls, 2023).