In a GPCR signaling cascade, how does a Gs protein increase intracellular cAMP levels?

• A. Gs activates adenylyl cyclase, converting ATP to cAMP, which activates PKA.
• B. Gs inhibits adenylyl cyclase.
• C. Gs directly phosphorylates proteins to increase cAMP.
• D. Gs activates guanylate cyclase.

Answer: (A)

When a GPCR activates a Gs protein, the Gs alpha subunit becomes active and directly stimulates adenylyl cyclase. Adenylyl cyclase then converts ATP into cyclic AMP, raising intracellular cAMP levels. The increase in cAMP binds to the regulatory subunits of protein kinase A (PKA), releasing the catalytic subunits to phosphorylate various target proteins and elicit cellular responses. This pathway contrasts with options that would inhibit adenylyl cyclase, directly phosphorylate proteins without cAMP, or activate guanylate cyclase to make cGMP.