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 Cylic AMP Pathway

Cyclic AMP (cAMP) is an important second messenger. Cyclic AMP mediates downstream activity of protein kinase A (PKA), exchange protein directly activated by cAMP (EPAC) and calcium flux through L-type calcium channels. Calcium is an important second messenger in cell signaling.

The level of cAMP is regulated by the action of a family of adenylate (adenylyl) cyclases that respond to G-protein subunits, especially Galphas and Galphai, which increase and decrease AC activity respectively. Specific heterotrimeric G-proteins are associated with a wide range of G-protein coupled receptors. Consequently, the level of cAMP can be modulated up or down depending upon which GPCRs are activated. Adenylyl cyclase activity is sometimes regulated by calcium and/or protein kinase C. The effects of calcium or PKC on adenylyl cyclase are isoform specific. The level of cAMP is regulated by its hydrolysis to 5’-AMP by cAMP phosphodiesterases (PDE). Various growth factor tyrosine kinase receptors activate PDE via a pathway that follows the receptor tyrosine kinase-PI3K-PDK-Akt/PBD-PDE axis. PDE is a direct substrate of AKT.