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[Biochemistry](https://durgical.com/en/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.

**Also called**
cAMP-dependent protein kinase

**EC number**
[2.7.11.11](https://www.enzyme-database.org/query.php?ec=2.7.11.11)

**Genes**
PRKACA, PRKAR1A

**Structure (PDB)**
[4WB5](https://www.rcsb.org/structure/4WB5)

## 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

- [Glycogen metabolism](https://durgical.com/en/biochemistry/pathways/glycogen-metabolism/)
- [Gluconeogenesis](https://durgical.com/en/biochemistry/pathways/gluconeogenesis/)

## Related conditions

- [Cushing syndrome](https://durgical.com/en/conditions/cushing-syndrome/)

## Related

- [Cyclic AMP (cAMP)](https://durgical.com/en/biochemistry/molecules/cyclic-amp/)
- [Adenylyl cyclase](https://durgical.com/en/biochemistry/enzymes/adenylyl-cyclase/)
- [G protein-coupled receptors and cAMP](https://durgical.com/en/biochemistry/topics/g-protein-coupled-receptors-and-camp/)
- [Glucagon signalling](https://durgical.com/en/biochemistry/topics/glucagon-signalling/)
- [Glycogen phosphorylase](https://durgical.com/en/biochemistry/enzymes/glycogen-phosphorylase/)
- [Glycogen synthase](https://durgical.com/en/biochemistry/enzymes/glycogen-synthase/)
- [Hormone-sensitive lipase (HSL)](https://durgical.com/en/biochemistry/enzymes/hormone-sensitive-lipase/)
- [Pyruvate kinase](https://durgical.com/en/biochemistry/enzymes/pyruvate-kinase/)
- [Acetyl-CoA carboxylase (ACC)](https://durgical.com/en/biochemistry/enzymes/acetyl-coa-carboxylase/)
- [Tyrosine hydroxylase](https://durgical.com/en/biochemistry/enzymes/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.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [PRKACA: cAMP-dependent protein kinase catalytic subunit alpha (human)](https://www.uniprot.org/uniprotkb/P17612/entry) (UniProt, 2026); [4WB5: Crystal structure of human cAMP-dependent protein kinase A (catalytic alpha subunit)](https://www.rcsb.org/structure/4WB5) (RCSB Protein Data Bank, 2026); [PRKAR1A gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/prkar1a/) (MedlinePlus, US National Library of Medicine, 2026); [Carney complex: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/carney-complex/) (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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