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The cAMP Branch: Adenylyl Cyclase and Protein Kinase A

Follow the Gs/Gi pathway from start to finish: how adenylyl cyclase makes cyclic AMP, how cAMP wakes up protein kinase A, and how that single enzyme reshapes the cell by adding phosphate tags.

Making the messenger

When a Gs protein is switched on, it travels to the membrane enzyme adenylyl cyclase and turns it on. Adenylyl cyclase takes ATP — the cell's energy currency — and snips it into cyclic AMP (cAMP), a small ring-shaped molecule that diffuses freely through the cytoplasm. cAMP is the classic second messenger: it carries the receptor's message deep into the cell.

The opposing Gi protein does the reverse: it dampens adenylyl cyclase, so cAMP levels fall. Because Gs and Gi push the same enzyme in opposite directions, the cell's cAMP level at any moment is a running balance of stimulating and inhibiting signals arriving at its surface.

From messenger to action: protein kinase A

cAMP itself does not do the cell's work — it has one main job: to wake up protein kinase A (PKA). A kinase is an enzyme that attaches a phosphate group onto other proteins, and that little tag flips those proteins on or off. When cAMP rises, it releases PKA's active core, which then phosphorylates a long list of target proteins — the true effectors of the cell.

In a heart cell, PKA phosphorylates calcium channels and pumps so the cell contracts harder and faster — which is exactly what an agonist at the beta-adrenoceptor (a Gs-linked GPCR) achieves. In a fat cell, the same PKA tells the cell to break down stored fat. One messenger, one kinase, but many tissue-specific outcomes, because each cell type owns a different set of target proteins.

Agonist -> beta-adrenoceptor -> Gs ON
   Gs -> adenylyl cyclase ON
      ATP -> cAMP (second messenger, rises)
         cAMP -> protein kinase A ON
            PKA adds phosphate to target proteins
               => stronger, faster heart contraction

(Gi pathway runs the same line in reverse: cAMP falls)
The full Gs/cAMP/PKA cascade in a heart cell.