Protein Kinase A
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Transcript of Protein Kinase A
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cAMP-dependent pathway
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cAMP
Cyclic nucleotide-gated ion channels (CNG)
Exchange proteins activated by cAMP (EPAC)
An enzyme called protein kinase A (PKA)
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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
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Deactivators of cAMP pathway
cAMP phosphodiesterase
Gi protein
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P r o te in O H + A T P P r o te in O P
O
O
O
+ A D P
P i H 2 O
P r o te in K in a s e
P r o te in P h o s p h a t a s e
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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)
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Inactivation
Catalytic subunit itself can be down-regulated by phosphorylation.
A feedback mechanism: One of the substrates that are activated by the kinase is a phosphodiesterase.
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Anchorage
A-kinase anchor protein (AKAP)
As a localizer: Regulatory subunits Cytoskeleton
As a signal modulator: Catalytic subunits Phosphodiesterase
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Heart
Vessels
Skeletal muscles
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Adipocytes and hepatocytes
Adrenaline and glucagon
Phosphorylation of acetyl-CoA carboxylase and pyruvate dehydrogenase
Inhibition of lipogenesis and promoting net gluconeogenesis
Insulin decreases the level of phosphorylation of these enzymes
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Nucleus accumbens
Helps transfer/translate the dopamine signal into cells
Reward and motivation
Smokers
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Principal cells in kidney
• V2 receptor
• Exocytosis of aquaporin 2 to apical membrane
• Synthesis of aquaporin 2
• Phosphorylation of aquaporin 2
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Medullary collecting duct
V2 receptor
Stimulate urea transporter 1
Urea transporter 1 exocytosis
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Proximal convoluted tubule
PTH receptor 1
Inhibit NHE3 ↓ H+ secretion
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Juxtaglomerular cell
β-receptor
Dopamine receptor
Glucagon receptor
Renin secretion
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Thank You!