A candidate targeting molecule of insulin-like growth factor-I receptor for gastrointestinal cancers

Figure 2 Insulin-like growth factor/type I insulin-like growth factor receptor and insulin/insulin receptor systems. Growth hormone-releasing hormone (GHRH) can stimulate secretion of growth hormone (GH), which upregulates insulin-like growth factors (IGFs) expression. IGF-I and IGF-II, which have about 40% sequence similarity to pro-insulin, predominantly activate type I IGF receptor (IGF-IR), which is a similar structure to insulin receptor (InsR) (59% sequence similarity). IGF-II is able to bind IR and both IGFs can bind hybrid IGF-IR/IR receptors. Ligand supply of both IGFs is regulated by two components. One is IGF binding proteins, which comprise at least six proteins [IGF binding protein (IGFBP)-1~6]. Another is IGF-IIR (lacks tyrosine kinase activity), which internalizes IGF-II for degradation in the pre-lysosomal compartment. Insulin can activate both IR and hybrid IGF-IR/InsR. Two isoforms of InsR exist, the A-isoform (InsR-A) and the B-isoform (InsR-B).