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).

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.

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.

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.

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

Sources: INSR: Insulin receptor (human) (UniProt, 2026); INSR gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); 1IR3: PHOSPHORYLATED INSULIN RECEPTOR TYROSINE KINASE IN COMPLEX WITH PEPTIDE SUBSTRATE AND ATP ANALOG (RCSB Protein Data Bank, 2026); Multiple endocrine neoplasia: 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.