Protein kinase A (PKA) is an enzyme involved in the cAMP-dependent pathway. It is activated when cyclic AMP (cAMP) levels rise in response to stimuli like hormones or neurotransmitters. PKA then directly phosphorylates other proteins to regulate various cellular processes either rapidly through direct phosphorylation or slowly through activating transcription factors. PKA activity is regulated by anchoring proteins and feedback loops, and it functions in many tissues to modulate processes like metabolism, ion transport, gene expression, and more.

1. Protein
Kinase A
cAMP-
Dependent
Protein Kinase
By: Vahid Nikoui
Email: nikoui@razi.tums.ac.ir

2. cAMP-dependent pathway

4. cAMP
 Cyclic nucleotide-gated ion channels
(CNG)
 Exchange proteins activated by cAMP
(EPAC)
 An enzyme called protein kinase A
(PKA)

5. Activators of cAMP pathway
• Cholera toxin:
• Increase cAMP levels
• Forskolin and fluoride:
• Activate adenylyl cyclase
• Caffeine, theophylline and bucladesine:
• Inhibit cAMP phosphodiesterase
• Pertussis toxin:
• Increase cAMP levels

6. Deactivators of cAMP
pathway
 cAMP phosphodiesterase
 Gi protein

7. Protein Kinase O
Protein OH + ATP Protein O P O + ADP
O
Pi H2O
Protein Phosphatase

8. PKA
• Direct protein phosphorylation
• PKA directly either increases or decreases
the activity of a protein (Rapid)
• Protein synthesis
• PKA first directly activates CREB, which
binds the cAMP response element (CRE)
(Slow)

11. Inactivation
 Catalyticsubunit itself can be down-
regulated by phosphorylation.
A feedback mechanism: One of the
substrates that are activated by the
kinase is a phosphodiesterase.

12. Anchorage
 A-kinase anchor protein (AKAP)
 As a localizer:
 Regulatory subunits
 Cytoskeleton
 As a signal modulator:
 Catalytic subunits
 Phosphodiesterase

13. Heart
Vessels
Skeletal muscles

14. Adipocytes and hepatocytes
 Adrenaline and glucagon
 Phosphorylationof acetyl-CoA carboxylase and
pyruvate dehydrogenase
 Inhibition
of lipogenesis and promoting net
gluconeogenesis
 Insulin
decreases the level of phosphorylation of
these enzymes

15. Nucleus accumbens
 Helps transfer/translate the dopamine signal into
cells
 Reward and motivation
 Smokers

16. Principal cells in kidney
• V2 receptor
• Exocytosis of aquaporin 2 to apical membrane
• Synthesis of aquaporin 2
• Phosphorylation of aquaporin 2

17. Medullary collecting duct
 V2 receptor
 Stimulate urea transporter 1
 Urea transporter 1 exocytosis

18. Proximal convoluted tubule
 PTH receptor 1
 Inhibit NHE3 ↓ H+ secretion

19. Juxtaglomerular cell
 β-receptor
 Dopamine receptor
 Glucagon receptor
 Renin secretion

21. Thank
You!