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[Biochemistry](https://durgical.com/en/biochemistry/) · Topic

# JAK–STAT pathway

Receptors for cytokines and some hormones (GH, prolactin, leptin, erythropoietin) use attached JAK kinases and STAT factors.

Updated 2026-11-01

## Key facts

- The receptor has no kinase activity of its own: JAK kinases (JAK1, JAK2, JAK3, TYK2) are bound to it.
- When the hormone binds, the JAKs phosphorylate each other and phosphorylate receptor tyrosines, where STAT proteins dock.
- Phosphorylated STATs form dimers, enter the nucleus and switch on genes: a short route from membrane to DNA.
- The JAK2 V617F mutation keeps the kinase on and causes polycythaemia vera and other myeloproliferative neoplasms.

## In detail

- Growth hormone, prolactin, leptin, erythropoietin, thrombopoietin, interferons and many interleukins use this pathway.
- Ligand binding shifts the two receptor chains and brings the JAKs close, which activate each other by transphosphorylation.
- STATs bind receptor phosphotyrosines through their SH2 domain, are phosphorylated by the JAKs and let go.
- In the nucleus STAT dimers bind specific DNA sequences; for example, GH activates STAT5 in the liver and raises IGF-1 output.
- Brakes: SOCS proteins, induced by the same signal, block the JAKs (negative feedback); phosphatases and PIAS proteins also act.

## Clinical notes

- JAK inhibitors are used in myelofibrosis, rheumatoid arthritis and other inflammatory diseases.
- Lack of JAK3 or of the common γ chain of interleukin receptors causes severe combined immunodeficiency.
- GH receptor defects (Laron syndrome): short stature with high GH and low IGF-1.
- Leptin resistance in obesity is linked in part to more SOCS3 in the hypothalamus.

## Drugs that act here

- [Tofacitinib](https://durgical.com/en/pharmacology/tofacitinib/)
- [Baricitinib](https://durgical.com/en/pharmacology/baricitinib/)
- [Ruxolitinib](https://durgical.com/en/pharmacology/ruxolitinib/)

## Related conditions

- [Rheumatoid arthritis](https://durgical.com/en/conditions/rheumatoid-arthritis/)
- [Adenosine deaminase deficiency (ADA-SCID)](https://durgical.com/en/conditions/adenosine-deaminase-deficiency/)
- [Obesity](https://durgical.com/en/conditions/obesity/)

## Related

- [Receptor tyrosine kinases](https://durgical.com/en/biochemistry/topics/receptor-tyrosine-kinases/)
- [Leptin, appetite and obesity](https://durgical.com/en/biochemistry/topics/leptin-appetite-and-obesity/)
- [Hormone classes and mechanisms](https://durgical.com/en/biochemistry/topics/hormone-classes-and-mechanisms/)

## Test yourself

Think of the answer, then tap the question to see it.

## How does a JAK–STAT receptor differ from a receptor tyrosine kinase?

It has no kinase domain of its own; it uses JAK kinases bound to its cytoplasmic part.

## Which JAK2 mutation causes polycythaemia vera?

V617F, which keeps JAK2 on without erythropoietin.

## Which proteins brake the JAK–STAT pathway by negative feedback?

SOCS proteins, induced by the signal itself, which block the JAKs.

## Which pituitary hormone uses JAK2–STAT5 to raise liver IGF-1?

Growth hormone (GH).

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

Sources: [JAK2 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/jak2/) (MedlinePlus, US National Library of Medicine, 2026); [Polycythemia vera: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/polycythemia-vera/) (MedlinePlus, US National Library of Medicine, 2026); [JAK2: Tyrosine-protein kinase JAK2 (human)](https://www.uniprot.org/uniprotkb/O60674/entry) (UniProt, 2026); [6VGL: JAK2 JH1 in complex with ruxolitinib](https://www.rcsb.org/structure/6VGL) (RCSB Protein Data Bank, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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