Cyclic AMP-dependent protein kinase A (PKA)

Cyclic AMP-dependent protein kinase A (PKA) is a ubiquitous serine/threonine kinase that serves as the primary effector for the second messenger cyclic adenosine monophosphate (cAMP) [1]. In its inactive state, the PKA holoenzyme exists as a tetramer composed of two regulatory subunits and two catalytic subunits; upon cAMP binding, the catalytic subunits are released to phosphorylate a wide array of cytoplasmic and nuclear targets, including the cAMP-response element-binding (CREB) protein [2][11]. This signaling pathway is critical for regulating diverse physiological processes such as glucose and lipid metabolism, cardiac muscle contraction, and long-term memory formation [3][5]. Dysregulation of PKA activity is linked to several pathologies, including endocrine disorders like Carney complex and Cushing's syndrome, as well as various cancers and cardiovascular diseases [4][10]. While direct therapeutic targeting of PKA has been challenging due to its broad functional profile and potential for systemic toxicity, the pathway is frequently modulated indirectly using phosphodiesterase (PDE) inhibitors and cAMP analogs [4][12]. Understanding the spatial and temporal regulation of PKA remains a major focus for drug development in metabolic and oncological contexts [6].

Other names

Protein kinase AcAMP-dependent protein kinasecAPKAdenosine cyclic monophosphate-dependent protein kinasePKA holoenzyme

Activation by cyclic AMP (cAMP) binding to regulatory subunits, which induces a conformational change and releases active catalytic subunits to phosphorylate serine and threonine residues on target proteins.