Insulin-like growth factor 1 resistance
The IGF1R gene at 15q26.3 codes for the 1367 amino acid peptide insulin-like growth factor 1 receptor. This is a receptor tyrosine kinase which binds insulin-like growth factor 1 (IGF1) with high affinity and IGF2 and insulin with a lower affinity. The gene product is cleaved into:
- Insulin-like growth factor 1 receptor alpha chain
- Insulin-like growth factor 1 receptor beta chain
IGF1 binding to one dimer results in trans autophosphorylation of tyrosine residues on the other subunit in a sequential manner; first Tyr-1165 is predominantly phosphorylated then Tyr-1161 and Tyr-1166 to optimise kinase activity. Activated insulin-like growth factor 1 receptor is key to cell growth and survival.
Mutations of IGF1R cause insulin-like growth factor 1 resistance (IGF1RES, OMIM:270450) with intrauterine growth retardation, poor postnatal growth and increased plasma insulin-like growth factor 1 levels.