Insulin Receptor
The insulin receptor (INSR) is a disulfide-linked heterotetramer composed of two extracellular alpha chains that bind insulin and two transmembrane beta chains carrying the tyrosine kinase domains. Ligand binding triggers a conformational rearrangement that activates the kinase, leading to autophosphorylation and phosphorylation of IRS proteins, which propagate signals through the PI3K/AKT and MAPK pathways to promote glucose uptake, metabolism, and cell growth. Alternative splicing produces isoform A, prominent in fetal tissues and cancer cells, and isoform B, dominant in metabolic tissues. Mutations disrupting receptor function cause severe inherited insulin-resistance syndromes such as Rabson-Mendenhall syndrome and Donohue syndrome.
