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

# Receptor tyrosine kinases

Receptors that are enzymes: when they bind the hormone they phosphorylate tyrosines and switch on growth and metabolic pathways.

Updated 2026-11-01

## Key facts

- Ligands: insulin, IGF-1, EGF, PDGF, VEGF, FGF and NGF.
- The ligand brings two receptors together (the insulin receptor is already a dimer) and each phosphorylates the other on tyrosines: trans-autophosphorylation.
- Phosphotyrosines are docking sites for proteins with SH2 domains (Grb2, PI3K, PLC-γ).
- Two main pathways: Ras → Raf → MEK → ERK (proliferation) and PI3K → Akt → mTOR (survival, metabolism and protein synthesis).

## In detail

- Each receptor has an outer ligand-binding domain, a single transmembrane helix and an inner kinase domain.
- After dimerisation the kinase is phosphorylated in its activation loop and becomes fully active; it then phosphorylates other tyrosines of the receptor itself.
- Grb2 binds a phosphotyrosine and brings SOS, which swaps GDP for GTP on Ras; Ras-GTP starts the MAP kinase cascade and ERK enters the nucleus.
- PI3K makes PIP3, which recruits Akt to the membrane; Akt phosphorylates dozens of targets (GSK3, FoxO, TSC2).
- The signal ends through tyrosine phosphatases, PTEN (which breaks down PIP3), Ras GTPase activity and receptor endocytosis.

**Also called**
RTK

## Clinical notes

- HER2 amplification in breast cancer and EGFR mutations in lung cancer: targets for antibodies and tyrosine kinase inhibitors.
- Activating KRAS mutations (common in pancreatic and colorectal cancer) keep Ras bound to GTP.
- Activating mutations of the RET receptor cause multiple endocrine neoplasia type 2 (medullary thyroid carcinoma, phaeochromocytoma).
- Loss of PTEN leaves Akt switched on and favours several tumours.

## Related conditions

- [Breast cancer](https://durgical.com/en/conditions/breast-cancer/)
- [Lung cancer](https://durgical.com/en/conditions/lung-cancer/)
- [Colorectal cancer](https://durgical.com/en/conditions/colorectal-cancer/)
- [Pancreatic cancer](https://durgical.com/en/conditions/pancreatic-cancer/)
- [Thyroid cancer (papillary)](https://durgical.com/en/conditions/thyroid-cancer/)

## Related

- [Insulin receptor](https://durgical.com/en/biochemistry/enzymes/insulin-receptor/)
- [Insulin signalling](https://durgical.com/en/biochemistry/topics/insulin-signalling/)
- [mTOR (mechanistic target of rapamycin)](https://durgical.com/en/biochemistry/enzymes/mtor/)
- [JAK–STAT pathway](https://durgical.com/en/biochemistry/topics/jak-stat-pathway/)
- [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.

## What does trans-autophosphorylation mean in a receptor tyrosine kinase?

The two halves of the dimerised receptor phosphorylate each other on tyrosines, which activates the kinase.

## Which adaptor protein links the phosphorylated receptor to Ras?

Grb2, which binds the phosphotyrosine through its SH2 domain and recruits SOS, the Ras activator.

## What is the effect of an activating KRAS mutation?

Ras stays bound to GTP and drives proliferation even without growth factor.

## Which enzyme reverses the PI3K signal and is a tumour suppressor?

PTEN, a phosphatase that turns PIP3 back into PIP2.

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

Sources: [INSR: Insulin receptor (human)](https://www.uniprot.org/uniprotkb/P06213/entry) (UniProt, 2026); [INSR gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/insr/) (MedlinePlus, US National Library of Medicine, 2026); [1IR3: PHOSPHORYLATED INSULIN RECEPTOR TYROSINE KINASE IN COMPLEX WITH PEPTIDE SUBSTRATE AND ATP ANALOG](https://www.rcsb.org/structure/1IR3) (RCSB Protein Data Bank, 2026); [Multiple endocrine neoplasia: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/multiple-endocrine-neoplasia/) (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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