<p>Cyclic AMP (cAMP) is a key intracellular regulator of cell function in both prokaryotes and eukaryotes. One of the ways in which it regulates enzymes is by binding to and causing activation of cAMP-dependent protein kinases, which in turn activate or deactivate other enzymes by phosphorylating them [<cite idref="PUB00002494"/>].</p><p> In the absence of cAMP, Protein Kinase A (PKA) exists as an equimolar tetramer of regulatory (R) and catalytic (C) subunits [<cite idref="PUB00007194"/>]. In addition to its role as an inhibitor of the C subunit, the R subunit anchors the holoenzyme to specific intracellular locations and prevents the C subunit from entering the nucleus. All R subunits have a conserved domain structure consisting of the N-terminal dimerization domain, inhibitory region, cAMP-binding domain A and cAMP-binding domain B. R subunits interact with C subunits primarily through the inhibitory site. The cAMP-binding domains show extensive sequence similarity and bind cAMP cooperatively.</p><p> Two types of R subunit exist - Type I and Type II - which differ in molecular weight, sequence, autophosphorylation cabaility, cellular location and tissue distribution. Types I and II were further sub-divided into alpha and beta subtypes, based mainly on sequence similarity. Type I does not undergo such autophosphorylation, but it can be phosphorylated slowly in vitro by cGMP-dependent protein kinases [<cite idref="PUB00000278"/>].</p><p>cAMP-dependent protein kinases are activated by the binding of two cAMP molecules to specific areas at the C terminus of each regulatory subunit of the enzyme. This causes in a conformational change in the structure, resulting in dissociation of the active catalytic domain from the regulatory domains.</p>