The insulin-like growth factor family of ligands, receptors, and binding proteins

The insulin-like growth factors (IGFs) have important roles in normal cellular growth and development. The IGFs have also been implicated in regulation of tumor cell growth. Two ligands, IGF-I and IGF-II, have been identified that are expressed in both fetal and adult tissues. They interact with at least two specific cell surface receptors. The type I IGF receptor is homologous to the insulin receptor in structure and has tyrosine kinase activity. The type II receptor is identical to the mannose-6-phosphate receptor known to be important in the trafficking of lysosomal enzymes; its role in IGF signal transduction is not clear. Furthermore, a hybrid receptor composed of subunits from the insulin receptor and the type I IGF receptor have been identified. In addition to these receptors, six different IGF binding proteins have been identified, which modulate the activity of the IGFs in various ways. Thus, there is great potential for complex interactions between the family members that could ultimately regulate normal and neoplastic cell growth.