cAMP-dependent Protein Kinase Pathways

Extracellular ligands or first messengers cannot enter cells directly. Instead, they bind GPCRs to stimulate G proteins, which activate enzymes such as adenylyl cyclase releasing large amounts of the second messenger, cyclic AMP.

The cyclic AMP transmits and amplifies signals mainly by activating protein kinase A or PKA.

The binding of one cyclic AMP molecule helps more cyclic AMPs bind the regulatory subunits of PKA. The resulting conformational change releases PKA catalytic subunits.

The activated PKA rapidly phosphorylates cytosolic target proteins, such as phosphorylase kinase and glycogen synthase, activating or inhibiting them. This prevents glucose to glycogen conversion and mobilizes glucose into the body.

Activated PKA also enters the nucleus and phosphorylates cyclic AMP response element-binding protein or CREB.

Phosphorylated CREB binds the cyclic AMP response element, or CRE on target genes and initiates the transcription of enzymes for glucose synthesis, thus restoring glucose levels.