The second messenger cyclic AMP (cAMP) mediates diverse cellular responses to external signals such as proliferation, ion transport, regulation of metabolism and gene transcription by activation of the cAMP-dependent protein kinase (cAPK or PKA). Activation of PKA occurs when cAMP binds to the two regulatory subunits of the tetrameric PKA holoenzyme resulting in release of active catalytic subunits. Three catalytic (C) subunits have been identified, designated Calpha, Cbeta and Cgamma , that each represent specific gene products. Calpha and Cbeta are closely related (93% amino acid sequence similarity), whereas Cgamma displays 83% and 79% similarity to Calpha and Cbeta, respectively.