Gene expression regulated by protein phosphorylation and cAMP. Cyclic AMP–dependent protein kinase A (PKA) is repressed by a regulatory subunit of the adenylyl cyclase holoenzyme and becomes active only on binding of cAMP to this subunit. The cAMP is produced when a signal molecule binds a transmembrane receptor and induces it to activate adenylyl cyclase. (Several steps are omitted here.) Once active, PKA catalytic subunits enter the nucleus and phosphorylate various target proteins, such as CREB, which then recruits RNA polymerase to DNA.