protein kinase a

Protein Kinase A

cAMP-Dependent Protein Kinase

By: Vahid NikouiEmail: 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

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

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

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.

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

Phosphorylation of 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!