Insulin-like growth factor 1 and Insulin-like growth factor 2 (IGF-1, IGF-2)

Insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 2 (IGF-2) are structurally related single-chain polypeptide hormones sharing close homology with proinsulin. IGF-1 consists of 70 amino acids, while IGF-2 contains 67 amino acids; both are mainly liver-derived and act as systemic growth-promoting factors, mediating the action of growth hormone (IGF-1) or acting as key fetal growth regulators (IGF-2). These growth factors bind primarily to the IGF1 receptor (IGF1R), a receptor tyrosine kinase, but can also interact (at lower affinity) with the insulin receptor isoform A (IR-A), and IGF2 can also bind IGF2R (a clearance receptor). IGF-1 and IGF-2 stimulate cell proliferation, differentiation, and survival in many tissues, and are implicated in both normal physiology—such as growth, organ development and metabolism—and in disease states, particularly cancer, where their signaling promotes tumor growth and survival. Circulating levels and tissue activity of IGFs are tightly regulated by a family of IGF binding proteins (IGFBPs) and other modulators.

Other names

IGF-1: Somatomedin C, IGF-IIGF-2: IGF-IIBoth: Insulin-like growth factors, IGFs

Agonists (replacement therapy): mimic IGF-1 at the IGF1R to restore growth signaling; Antagonists/monoclonal antibodies: block IGF-1 or IGF-2 binding to IGF1R or IR-A, inhibiting downstream mitogenic and survival signaling, mainly in cancer settings; Tyrosine kinase inhibitors: inhibit receptor activation and downstream pathways like PI3K/AKT and MAPK