Cyclic adenosine monophosphate-dependent protein kinase A signaling pathway (cAMP-PKA pathway) (cAMP-PKA pathway)

The Cyclic adenosine monophosphate-dependent protein kinase A (cAMP-PKA) signaling pathway is a fundamental intracellular cascade that mediates the cellular response to various hormones and neurotransmitters (StatPearls, 2023). It is initiated by the activation of G protein-coupled receptors (GPCRs), which stimulate adenylyl cyclase to convert ATP into the second messenger cAMP (NCBI, 2022). cAMP then binds to the regulatory subunits of PKA, triggering the release of active catalytic subunits that phosphorylate a variety of proteins, including the transcription factor CREB, thereby modulating gene expression (UniProt, 2024). This pathway is vital for regulating processes such as glucose metabolism, cardiac function, and neuronal plasticity (PubMed, 2021). Dysregulation of cAMP-PKA signaling is implicated in several diseases, including Carney complex, Cushing's syndrome, and various malignancies (NIH, 2023). Drugs targeting this pathway often act by modulating cAMP levels through phosphodiesterase (PDE) inhibition or adenylyl cyclase activation (Nature Reviews Drug Discovery, 2022). However, the ubiquitous expression of pathway components presents significant challenges for achieving tissue-specific therapeutic effects without systemic toxicity (Journal of Clinical Investigation, 2020).

Other names

cAMP-dependent protein kinase signaling pathwayAdenylyl cyclase-cAMP-PKA axisCyclic AMP signaling cascadecAMP-PKA signaling

Modulation of intracellular cAMP levels and subsequent PKA activity through GPCR activation, adenylyl cyclase stimulation, or phosphodiesterase inhibition.