Hybrid Insulin Receptors: Molecular Mechanisms of Negative-Dominant Mutations in Receptor-Mediated Insulin Resistance
- Jonathan Whittaker, MD,
- Maria A Soos, PhD and
- Ken Siddle, PhD
- Division of Endocrinology and Metabolism, Department of Medicine, Health Sciences Center, State University of New York at Stony Brook New York Department of Clinical Biochemistry, University of Cambridge United Kingdom
- Address correspondence and reprint requests to Jonathan Whittaker, MD, Division of Endocrinology, Department of Medicine, Health Sciences Center T15-060, SUNY at Stony Brook, Stony Brook, NY 11794.
Abstract
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.
- Copyright © 1990 by the American Diabetes Association
