Insulin receptor family
insulin receptor family
Insulin receptors and the related receptor family members, IGF1 receptors and insulin receptor-related receptors are expressed at the cell surface as preformed heterotetramers, each comprising two hemi-receptors composed of one α- and one β-subunit. Each α- and β-subunit and the two α-subunits are cross-linked by disulphide bridges. The extracellular α subunits bind insulin or IGFs. The β-subunits have a tyrosine kinase domain. INSR and IGF1R have high sequence homology in the cytoplasmic tyrosine kinase domain, with greater divergence in the extracellular ligand-binding α-subunits. INSRRs have high homology with INSRs and IGF1Rs in the tyrosine kinase domain, but the extracellular α-subunit is divergent and does not bind insulin or IGFs. INSRRs operate as alkali sensors: exposure to extracellular alkaline pHo (pHo>8.0) causes a conformational change in the α subunit that activates the intracellular tyrosine kinase resulting in Tyr-phosphorylation of the β-subunit with activation of downstream signalling.