Type-2 IGF receptor: A multi-ligand binding protein

The Type-2 insulin-like growth factor receptor (IGF2R) is a ubiquitously expressed integral glycoprotein with a molecular mass of 300 kDa, Four different classes of ligands are presently known, binding to distinct sites at the extracytoplasmic receptor domain: mannose 6-phosphate-containing lysosomal enzymes, the non-glycosylated IGF II, retinoic acid, and urokinase-type plasminogen activator receptor. The intracellular transport and functions of the IGF2R are determined by signal structures localized in the cytoplasmic receptor domain interacting with different cytosolic and membrane-bound proteins. The IGF2R gene is developmentally regulated. The coordinated expression of IGF II and IGF2R in most mammalian tissues and gene targeting experiments suggest a role of IGF2R in the control of extracellular IGFII concentration by receptor-mediated endocytosis and subsequent degradation of the growth factor in lysosomes. Specific alterations in the expression, activation and routing of both IGF2R and its ligands in human and rodent tumors suggest that the IGF2R functions as a tumor suppressor.