Figure 1: Cyclic adenosine 3’, 5’ monophosphate (cAMP) signaling microdomains. In response to extra- or intracellular signals, cAMP is formed at discrete intracellular compartments or microdomains including the cell membrane, mitochondria and the nucleus. cAMP microdomains contain an adenylyl cyclase, either a transmembrane adenylyl cyclase (tmAC) or the soluble adenylyl cyclase (sAC), that forms cAMP from adenosine triphosphate (ATP); a phosphodiesterases (PDE) that metabolizes cAMP to adenosine monophosphate (AMP); and a cAMP effector protein such as protein kinase A (PKA), exchange protein activated by cAMP (EPAC) and cyclic nucleotide gated channels. tmAC-dependent signal transduction occurs at the cell membrane when (1) a ligand (e.g., epinephrine) binds its receptor (e.g., ß-adrenergic G-protein coupled receptor) and (2) the heterotrimeric G-protein activates the tmAC (3) to make cAMP. In intracellular microdomains (4) such as the nucleus and the mitochondria, cAMP is produced by sAC in response to changes in metabolism or pH. In either case, the cAMP signal is terminated when cAMP is catabolized to AMP by a PDE (5). Abbreviations: TCR, T cell receptor; tmAC, transmembrane adenylyl cyclase; sAC, soluble adenylyl cyclase; cAMP, cyclic adenosine monophosphate; ATP, adenosine triphosphate; AMP, adenosine monophosphate; PDE, phosphodiesterase