Insulin-like growth factor receptor

Insulin-like growth factor receptors (IGFR) are transmembrane receptors which are stimulated by insulin-like growth factors (IGF). IGFR contains 2 extracellular α chains and 2 transmembranal β chains. Upon binding of IGF, a tyrosine in the β chain becomes autophosphorylated and triggers a cascade of intracellular signaling. The insulin-like growth factor 1 (IGF-1) receptor belongs to the large class of tyrosine kinase receptors. See also IGF1, Growth factors and Kinase-linked, enzyme-linked and related receptors.

• Insulin-like growth factor receptor 1 is the mediator of the anabolic and mitogenic activity of growth hormone^[1]
  
• Insulin-like growth factor receptor 2 is a protein hormone regulating cell proliferation, growth, migration, differentiation and survival^[2]
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Memory-Enhancement by Traditional Chinese Medicine? ^[3]

Cognitive impairment is an emerging issue and increasing research points to the significant role of insulin-like growth factor I (IGF-I) in cognitive brain functions. IGF receptor (IGF-IR, PDB ID: 3i81, colored in darkmagenta) activation is critical for IGF-I to elicit desirable cognitive functions. Traditional Chinese medicine (TCM) ligands 3-(2-carboxyphenyl)-4(3H)-quinazolinone (orgin: Isatisin digotica, colored in green), (+)-N-methyllaurotetanine (origin: Lindera aggregate, colored in deeppink), and (+)-1(R)-Coclaurine (origin: Nelumbonucifera Gaertn, colored in salmon) showed high binding affinity towards IGF-IR at the binding site defined by the control in PDB ID: 3i81. Molecular dynamics simulation revealed that the TCM ligands were secured at the opening of the IGF-IR binding site for the duration of the MD. 3-(2-carboxyphenyl)-4(3H)-quinazolinone was stabilized by Asp1056, (+)-N-methyllaurotetanine was stabilized by Leu975 and Asp1056, and (+)-1(R)-Coclaurine was stabilized by Leu975 and Gly1055 (key residues are colored in yellow). Four different quantitative-structure activity relationship models consistently predicted bioactivity of the TCM ligands towards IGF-IR. In summary, the TCM candidates exhibit drug-like potential in both structural-based and ligand-based properties and may have potential for further applications in enhancing cognition.