The cAMP-dependent protein kinases and cAMP signal transduction

The cAMP signal transduction system is one of several second messenger-dependent pathways that generates intracellular responses to extracellular signals. The primary element in this cascade is the cAMP-dependent protein kinases (PKA), which mediate most cAMP actions by phosphorylation. Regulatory subunit isoforms bind cAMP and localize catalytic subunit isoforms near substrate proteins. C-subunit isoforms also may have specific roles in PKA function. Compared to the C alpha-subunit isoform, C gamma has a more limited distribution, a different substrate and inhibitor specificity, and appears to require higher levels of cAMP for activation. Many PKA isoforms with differing localization, regulatory, and kinetic properties are thus possible. The potential roles for R- and C-subunits are discussed in the broad context of cAMP/PKA-mediated cell function.