Biochemistry · Enzyme
Protein kinase A (PKA) !
The kinase that turns cAMP into action: it phosphorylates glycogen, fat and glucose enzymes during fasting and stress.
Updated 2026-11-01
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Key facts
- A tetramer of two regulatory (R) and two catalytic (C) subunits; each R binds two cAMP and lets go of its active C.
- It phosphorylates serines and threonines in Arg-Arg-X-Ser/Thr-type sequences.
- Activates: phosphorylase kinase, hormone-sensitive lipase, perilipin, tyrosine hydroxylase and CREB. Inactivates: glycogen synthase, liver pyruvate kinase and liver PFK-2.
- Structure 4WB5 is the human catalytic subunit with ATP and Mg²⁺ in the active site, next to the inhibitor peptide PKI sitting where the substrate goes.
Regulation
- cAMP frees the catalytic subunits by binding the regulatory ones.
- AKAP proteins anchor it near its substrates.
- Phosphodiesterase (breaks down cAMP) and the phosphatases PP1/PP2A reverse its effect; insulin activates both.
Inhibitors and toxins
- PKI (endogenous protein inhibitor, pseudosubstrate)
- cAMP-free regulatory subunits
- H-89 (experimental use)
Clinical notes
- Carney complex: loss of PRKAR1A leaves PKA on and causes cardiac myxomas, skin spots and Cushing syndrome from pigmented nodular adrenal disease.
- PKA explains why glucagon and adrenaline mobilise glycogen and fat within minutes.
- Activating PRKACA variants are found in cortisol-producing adrenal adenomas.
Pathways
Related conditions
Related
- Cyclic AMP (cAMP)
- Adenylyl cyclase
- G protein-coupled receptors and cAMP
- Glucagon signalling
- Glycogen phosphorylase
- Glycogen synthase
- Hormone-sensitive lipase (HSL)
- Pyruvate kinase
- Acetyl-CoA carboxylase (ACC)
- Tyrosine hydroxylase
Test yourself
Think of the answer, then tap the question to see it.
How does cAMP activate PKA?
It binds the regulatory subunits, which release the active catalytic subunits.
What does PKA do to glycogen synthase and to phosphorylase kinase?
It inactivates glycogen synthase and activates phosphorylase kinase: glycogen is broken down instead of made.
Which disease does loss of the PRKAR1A regulatory subunit cause?
Carney complex, with myxomas and adrenal Cushing syndrome.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: PRKACA: cAMP-dependent protein kinase catalytic subunit alpha (human) (UniProt, 2026); 4WB5: Crystal structure of human cAMP-dependent protein kinase A (catalytic alpha subunit) (RCSB Protein Data Bank, 2026); PRKAR1A gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Carney complex: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
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Representative model, for educational purposes only.