One major GPCR pathway uses cyclic AMP (cAMP) as a second messenger.

An activated stimulatory G protein can activate adenylyl cyclase, a membrane-associated enzyme that converts ATP into cAMP.

The signaling chain is

ligand → GPCR → G protein → adenylyl cyclase → cAMP → PKA

cAMP activates protein kinase A

Protein kinase A (PKA) is regulated by cAMP. In its inactive form, catalytic subunits are held by regulatory subunits. Binding of cAMP to the regulatory subunits changes the complex and releases active catalytic kinase subunits.

Active PKA can phosphorylate multiple target proteins, changing enzyme activity, ion-channel behavior, or gene regulation.

The pathway can amplify signal

One active receptor can activate multiple G proteins. One active adenylyl cyclase can make many cAMP molecules. One active PKA molecule can phosphorylate many substrate molecules.

Thus a small extracellular signal can produce a much larger intracellular response.

Termination requires several resets

The pathway does not stop merely because the ligand concentration falls.

• $G\alpha$ hydrolyzes GTP to GDP;
• phosphodiesterases degrade cAMP to AMP;
• phosphatases remove regulatory phosphates from PKA targets.

These reset steps determine signaling duration as well as signal onset.

Example: rapid metabolic response

If PKA phosphorylates an enzyme that promotes release of stored fuel, receptor activation can change fuel-handling reactions within seconds because the cell modifies proteins already present rather than waiting to synthesize new proteins.

The cAMP pathway therefore illustrates a general design principle: receptor-controlled production of a diffusible second messenger connects an extracellular signal to a reversible phosphorylation response.