cAMPSignale

cAMP signals refer to the cellular signaling pathways that use cyclic adenosine monophosphate (cAMP) as a second messenger. They translate extracellular cues, such as hormones and neurotransmitters, into intracellular responses across many tissues. The central biochemical step is the synthesis of cAMP from ATP by adenylyl cyclases, which are activated or inhibited by G protein-coupled receptors. Gs-coupled receptors stimulate adenylyl cyclase, increasing cAMP; Gi-coupled receptors inhibit it. Other inputs modulate AC activity, including different isoforms and subcellular localization.

cAMP exerts its effects primarily through two major classes of targets: protein kinase A and Epac. PKA is a holoenzyme consisting of regulatory and catalytic subunits; binding of cAMP releases the active catalytic subunits that phosphorylate multiple substrates, including enzymes, ion channels, and transcription factors. Epac acts as a guanine-nucleotide exchange factor for Rap GTPases, modulating processes such as vesicle trafficking and cytoskeletal dynamics. Additional cAMP targets include cyclic nucleotide-gated ion channels and other signaling proteins.

Signal duration and specificity are controlled by phosphodiesterases (PDEs), which hydrolyze cAMP to AMP, and by scaffolding proteins like AKAPs that create localized signaling microdomains. Through PKA and CREB-dependent pathways, cAMP signaling can influence gene expression and long-term cellular changes, including memory formation in neurons. In peripheral tissues, cAMP modulates glucose and lipid metabolism, heart muscle contraction, and hormone secretion.

The concept of cAMP as a key second messenger emerged in the work of Sutherland and Rall in the 1950s, establishing a paradigm for cyclic nucleotide signaling.