Substitution of lysine for asparagine at position 15 in the alpha-subunit of the human insulin receptor. A mutation that impairs transport of receptors to the cell surface and decreases the affinity of insulin binding.

摘要: Mutations in the insulin receptor gene can compromise ability of to mediate action. Previously, investigations a patient with genetic form resistance, we have identified mutant allele encoding an which lysine is substituted for asparagine at position 15 alpha-subunit. In present study, characterized Lys15-mutant expressed by transfection cDNA into NIH-3T3 cells. The Lys15-mutation causes least two defects function. First, mutation retards post-translational processing and impairs transport plasma membrane, thereby reducing number receptors on cell surface. Second, 5-fold reduction affinity bind insulin. These combine render target resistant normal physiological concentrations It seems likely that both functional associated be explained assuming distorts three-dimensional structure receptor. Presumably, abnormal conformation interferes through endoplasmic reticulum Golgi, also inhibits binding its site