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.

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.

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.

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).

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

Sources: JAK2 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Polycythemia vera: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); JAK2: Tyrosine-protein kinase JAK2 (human) (UniProt, 2026); 6VGL: JAK2 JH1 in complex with ruxolitinib (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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Representative model, for educational purposes only.