Biochemistry · Enzyme
Insulin receptor !
A receptor tyrosine kinase: insulin switches it on and it phosphorylates the proteins that move GLUT4 to the membrane and store glucose.
Updated 2026-11-01
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Key facts
- An α₂β₂ heterotetramer held by disulfide bridges; it is made from a single precursor chain cut in the Golgi apparatus.
- Insulin binds the (outer) α subunits; the (transmembrane) β subunits carry the kinase domain.
- Autophosphorylation of three activation-loop tyrosines (1158, 1162, 1163) switches the kinase on, and it phosphorylates IRS-1 and IRS-2.
- Structure 1IR3 is the phosphorylated human kinase with an ATP analogue (ANP), Mg²⁺ and a substrate peptide: it shows the active site at work.
Regulation
- Activation: insulin binding (and, with lower affinity, IGF-1 and IGF-2).
- Switched off by tyrosine phosphatases (PTP1B) and receptor endocytosis.
- Serine phosphorylation of IRS-1 (JNK, IKKβ, PKC, S6K1) weakens the signal in insulin resistance.
Inhibitors and toxins
- PTP1B (endogenous phosphatase that dephosphorylates the receptor)
- Antibodies against the receptor (type B insulin resistance)
Clinical notes
- Severe INSR mutations: Donohue syndrome (leprechaunism) and Rabson–Mendenhall syndrome, with very high insulin and growth problems.
- Type A insulin resistance (milder mutations) shows up in young women with acanthosis nigricans and hyperandrogenism.
- High insulin stimulates ovarian insulin and IGF-1 receptors and raises androgens, as in polycystic ovary syndrome.
Drugs that act here
- Isophane (NPH) insulin
- Insulin glargine
- Insulin lispro
- Insulin aspart
- Insulin degludec
- Insulin detemir
- Insulin glulisine
Related conditions
Related
- Insulin signalling
- Receptor tyrosine kinases
- mTOR (mechanistic target of rapamycin)
- Glycogen synthase
- Fed, fasting and starvation states
Test yourself
Think of the answer, then tap the question to see it.
What is the structure of the insulin receptor?
An α₂β₂ heterotetramer held by disulfide bridges; the β subunits carry the tyrosine kinase domain.
What happens right after insulin binds the receptor?
The β subunits phosphorylate each other on activation-loop tyrosines and the kinase phosphorylates IRS-1 and IRS-2.
Which phosphatase switches the insulin receptor off?
PTP1B, which dephosphorylates its tyrosines.
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); Donohue syndrome: 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.