# Protein Kinase A (PKA) **Protein Kinase A (PKA)** - A tetrameric (four) protein composed of two catalytic and two regulatory subunits - Inactive complex - When cAMP concentration is raised, the two catalytic subunits are released. In the nucleus, PKA phosphorylates CREB, which binds to cAMP response elements (CREs) in DNA, activating transcription of genes involved in gluconeogenesis, metabolism, and cell survival. ## Activation of Protein Kinase A 1. Cytosolic cAMP concentration increases. 2. Two cAMP molecules bind to each PKA regulatory subunit. 3. The regulatory subunits dissociate from the catalytic subunits. 4. The free catalytic subunits interact with proteins to phosphorylate Ser or Thr residues 5. Each regulatory subunit is activated as the two cAMP molecules release 6. Cytosolic cAMP concentration decreases --- **In Response to GPCR Activation:** - GPCR activation increases cAMP, which binds PKA’s regulatory subunits, causing their dissociation and activation of the catalytic subunits, allowing phosphorylation of target proteins. ### Impact of Activation