Insulin-like growth factor I (also known as somatomedin C and somatomedin A) and insulin-like growth factor II (multiplication stimulating activity or MSA) belong to the family of insulin-like growth factors that are structurally homologous to proinsulin. Mature IGF-I and IGF-II share approximately 70% sequence identity. Both IGF-I and IGF-II are expressed in many tissues and cell types and may have autocrine, paracrine and endocrine functions. Mature IGF-I and IGF-II are highly conserved (100% identity between human, bovine and porcine proteins) and exhibit cross-species activity.
IGF-II is a potent mitogenic growth factor. However, unlike IGF-I which has important postnatal roles, the growth-promoting function of IGF-II is limited to embryonic development.
Two specific cell surface receptors that bind IGF-I and IGF-II have been identified. The type I IGF receptor that participates in IGF signaling is structurally related to the insulin receptor. It is a disulfide-linked heterotetrameric transmembrane glycoprotein with an intracellular tyrosine kinase domain. Type I IGF receptor binds IGF-I with higher affinity than IGF-II. The type II IGF receptor which binds IGF-II with much higher affinity than IGF-I is also the cation-independent mannose 6-phosphate receptor. At the present time, it is not known if the type II IGF receptor participates in the IGF signaling pathway. An additional unknown receptor which mediates IGF-II signaling has also been proposed. Circulating IGFs exist in complexes bound to IGF binding proteins. Currently, at least six high affinity binding proteins have been identified.