protein kinase A

Protein kinase A is the chief lieutenant of cyclic AMP. Cyclic AMP itself does almost nothing directly to the cell's working parts; instead it activates protein kinase A, which carries out the orders by tagging other proteins with phosphate groups and thereby switching their activity on or off.

At rest protein kinase A is a four-part complex: two regulatory subunits holding two catalytic subunits inactive. When cyclic AMP rises, it binds the regulatory subunits and releases the catalytic subunits, which then phosphorylate serine and threonine residues on target proteins. Targets include metabolic enzymes (such as those controlling glycogen and fat breakdown), ion channels, and the gene-regulating protein CREB, which lets the signal reach into the nucleus and alter gene expression.

Because protein kinase A is the common output of every Gs-coupled, cyclic-AMP-raising signal, it explains the diverse downstream effects of beta-agonists, glucagon, and phosphodiesterase inhibitors. The action is reversed by phosphatases, which strip the phosphate groups back off — so the cell's state reflects a continuous balance between kinase and phosphatase activity.