Cross-talk with other pathways modulates signal amplitude and cell-type specificity further, and feedforward signalling by PKA increases PDE4.Indeed, both ACs and PDEs are positively and negatively regulated by numerous other signalling pathways, including calcium signalling (via calmodulin, CamKII, CamKIV, and calcineurin ), subunits of other G proteins (e.g., I o, and q proteins, and the subunits in some cases), inositol lipids (via PKC) (through the ERK MAP kinase and PKB).Alternatively, ligands that excite GPCRs linked to Gi can reduce AC action, while PDEs can breakdown cAMP.cAMP generated as a result of AC activation can activate several effectors, with cAMP-dependent protein kinase being the most thoroughly investigated (PKA).Some AC isoforms can also be stimulated by the subunits. s is released from heterotrimeric G-protein complexes in response to the binding of agonist ligands to GPCRs (epinephrine in the case of adrenoceptors), where it binds to and activates AC. Most ACs (soluble bicarbonate-regulated ACs are the exception) are activated by interactions with the subunit of the Gs protein (s) downstream of G-protein-coupled receptors (GPCRs) such as the adrenoceptor.Numerous genes encoding distinct isoforms of these enzymes differ in their expression patterns and regulatory mechanisms, hence generating cell-type and stimulus-specific responses.Two enzymes, adenylyl cyclase (AC) and cyclic nucleotide phosphodiesterase, regulate the intracellular concentration of cAMP (PDE).The first second messenger to be identified, cyclic adenosine 3′,5′-monophosphate (cAMP) performs key functions in cellular responses to numerous hormones and neurotransmitters (Sutherland and Rall 1958).The enzyme phosphodiesterase catalyses the breakdown of cAMP into AMP.Muscle adenylate cyclase responds more strongly to adrenaline than liver adenylate cyclase does to glucagon.Agonists of adenylate cyclase inhibitory G (Gi)-protein-coupled receptors inhibit adenylate cyclase.A variety of signalling substances activate adenylate cyclase via the activation of adenylate cyclase stimulatory G (Gs)-protein-coupled receptors.Cyclic AMP is produced from ATP by adenylate cyclase, which is positioned on the inner side of the plasma membrane and is anchored in multiple sites throughout the cell.EPAC (a guanine-nucleotide-exchange factor), cyclic-nucleotide-gated ion channels, and protein kinase A (which phosphorylates many metabolic enzymes) are its primary effectors.First discovered and named cAMP was the pioneer of the second messenger class.Adenosine triphosphate (ATP) is a nucleotide that can be broken down into cyclic adenosine monophosphate (cAMP), which is used for signal transduction within cells.The second messenger cyclic adenosine monophosphate (cAMP, cyclic AMP, or 3′,5′-cyclic adenosine monophosphate) is involved in a wide variety of essential biological processes.
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