Hybrid insulin receptors. Molecular mechanisms of negative-dominant mutations in receptor-mediated insulin resistance.
Certain syndromes of extreme insulin resistance are the result of negative-dominant mutations of the insulin receptor. The insulin-receptor heterotetramer appears to be the minimal functional unit for insulin signal transduction probably due to a requirement for intersubunit interactions. The observation that insulin and insulinlike growth factor I receptors can be found in hybrid heterotetramers suggests that insulin receptors can be composed of heterodimers that are the products of separate genes. Such a structure provides a potential molecular mechanism for negative-dominant receptor mutations.
Department of Medicine, Health Sciences Center, State University of New York, Stony Brook.
J
J
Whittaker
M A
MA
Soos
K
K
Siddle
D000818:Animals; D005799:Genes, Dominant; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D009154:Mutation; D055503:Protein Multimerization; D011972:Receptor, Insulin / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology
D011972:Receptor, Insulin