Cyclic AMP-dependent protein kinase (PKA) (PKA)

The Cyclic AMP-dependent protein kinase (PKA) pathway is a fundamental signal transduction mechanism that translates extracellular stimuli, such as hormones and neurotransmitters, into specific intracellular responses [StatPearls: Physiology, Adenosine Monophosphate]. The central effector, PKA, is a serine/threonine kinase that exists as an inactive heterotetramer until cyclic AMP (cAMP) binds to its regulatory subunits, triggering the release of active catalytic subunits [UniProt: P17612]. These subunits then phosphorylate a wide array of target proteins, most notably the cAMP response element-binding (CREB) protein, which enters the nucleus to modulate gene transcription related to metabolism, cell growth, and memory [PubMed: 30206190]. Dysregulation of this pathway is implicated in numerous pathologies, including Carney complex, Cushing's syndrome, and various malignancies where PKA subunits are mutated or overexpressed [PubMed: 24606322]. While direct PKA inhibitors like H-89 are primarily used as research tools, the pathway is a major therapeutic focus through the pharmacological modulation of upstream G protein-coupled receptors and downstream phosphodiesterases [PubMed: 28214325].

Other names

Protein kinase AcAMP-dependent protein kinaseAdenosine 3',5'-monophosphate-dependent protein kinase

Activation by cyclic AMP (cAMP) leading to the phosphorylation of serine and threonine residues on target proteins, such as CREB, to modulate cellular activity [StatPearls: Physiology, Adenosine Monophosphate].