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Protein
                                Kinase A


                                    cAMP-
                                 Dependent
                                Protein Kinase

      By: Vahid Nikoui
Email: nikoui@razi.tums.ac.ir
cAMP-dependent pathway
cAMP
 Cyclic   nucleotide-gated ion    channels
 (CNG)

 Exchange   proteins activated by cAMP
 (EPAC)

 An enzyme     called   protein   kinase   A
 (PKA)
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
Deactivators of cAMP
pathway

 cAMP    phosphodiesterase

 Gi   protein
Protein Kinase             O

Protein        OH + ATP      Protein      O   P   O   + ADP
                                              O
          Pi                        H2O
                 Protein Phosphatase
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)
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.
Anchorage

 A-kinase     anchor protein (AKAP)

 As   a localizer:
    Regulatory subunits
    Cytoskeleton

 As   a signal modulator:
    Catalytic subunits
    Phosphodiesterase
Heart

Vessels

Skeletal muscles
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
Nucleus accumbens



 Helps   transfer/translate the dopamine signal into
 cells

 Reward    and motivation

 Smokers
Principal cells in kidney

•   V2 receptor

•   Exocytosis of aquaporin 2 to apical membrane

•   Synthesis of aquaporin 2

•   Phosphorylation of aquaporin 2
Medullary collecting duct


 V2   receptor

 Stimulate   urea transporter 1

 Urea   transporter 1 exocytosis
Proximal convoluted tubule

 PTH   receptor 1

 Inhibit   NHE3     ↓ H+ secretion
Juxtaglomerular cell

 β-receptor


 Dopamine     receptor

 Glucagon     receptor



 Renin   secretion
Thank
You!

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Protein Kinase A

  • 1. Protein Kinase A cAMP- Dependent Protein Kinase By: Vahid Nikoui Email: nikoui@razi.tums.ac.ir
  • 3.
  • 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)
  • 9.
  • 10.
  • 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
  • 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
  • 20.