Protein kinase A regulatory subunit (PKA-R) (PKA-R)

Protein kinase A (PKA) regulatory subunits are critical components of the cAMP-dependent protein kinase complex, serving as the primary intracellular receptors for cyclic AMP (cAMP) (UniProt, 2024). These subunits exist as dimers that bind to two catalytic subunits to form an inactive holoenzyme. Each regulatory subunit possesses two tandem cAMP-binding domains; upon binding of cAMP, the regulatory subunits undergo a conformational change that releases the catalytic subunits, allowing them to phosphorylate downstream targets involved in metabolism, cell growth, and gene expression (Taylor et al., 2012). Mutations in the genes encoding these subunits, such as PRKAR1A, are linked to various pathologies, including Carney complex and Cushing syndrome, highlighting their role in endocrine regulation and tumor suppression (Stratakis, 2016). Pharmacological modulation of these subunits typically involves cAMP analogs, which are being explored for their potential in treating certain cancers and inflammatory conditions by specifically activating or inhibiting PKA signaling pathways (Cho-Chung, 2000).

Other names

cAMP-dependent protein kinase regulatory subunitPRKAR1APRKAR1BPRKAR2APRKAR2BPKA regulatory subunitcAMP-binding proteinPRKARPRKAR1PRKAR2

Allosteric activation of Protein Kinase A (PKA) through the binding of cyclic adenosine monophosphate (cAMP) or its analogs to the regulatory subunits, which induces a conformational change and the subsequent release of active catalytic subunits (Taylor et al., 2012; Cho-Chung, 2000).