IGF1R

IGF1R, or insulin-like growth factor 1 receptor, is a cell surface receptor tyrosine kinase that binds the ligands IGF-1 and IGF-2. It plays a central role in growth, development, and metabolism and is expressed widely in fetal and postnatal tissues.

The receptor is a heterotetramer composed of two alpha subunits and two beta subunits. It is synthesized as a single precursor that is cleaved to generate the extracellular alpha chains and the membrane-spanning beta chains, which contain the tyrosine kinase domain. Ligand binding to the extracellular domain induces receptor autophosphorylation in the beta subunits, which activates the kinase activity and initiates intracellular signaling.

IGF1R signaling primarily engaging the PI3K–AKT and MAPK/ERK pathways promotes cell survival, growth, proliferation, and protein synthesis. Adaptor proteins such as IRS1/2 and SHC couple the receptor to downstream signaling cascades. The receptor also exhibits crosstalk with the insulin receptor and can form hybrid receptors that modulate signaling outputs. Regulation occurs through IGF-binding proteins that control ligand availability and through negative feedback loops and phosphatases that dampen signaling.

Functionally, IGF1R is essential for normal embryonic development and is important for postnatal growth and metabolism. Dysregulation or overexpression of IGF1R has been associated with cancer progression and resistance to therapy, leading to interest in therapeutic targeting. Strategies include monoclonal antibodies against IGF1R and tyrosine kinase inhibitors that target IGF1R and related receptors; these approaches face challenges such as metabolic side effects and compensatory signaling.

The IGF1R gene in humans is located on chromosome 15q26.3. The receptor’s activity is modulated by the broader IGF axis, including IGF ligands and binding proteins that regulate ligand availability and signaling strength.