Gu J L, Goldfine I D, Forsayeth J R, De Meyts P
Department of Diabetes, Endocrinology and Metabolism, City of Hope National Medical Center, Duarte, CA 91010.
Biochem Biophys Res Commun. 1988 Jan 29;150(2):694-701. doi: 10.1016/0006-291x(88)90447-0.
Two monoclonal antibodies to the insulin receptor, MA-5 and MA-20, unlike other monoclonal antibodies, do not mimick the accelerating effect of insulin on the dissociation of 125I-insulin from the receptors (negative cooperativity). On the contrary, MA-5 and MA-20 markedly slow down the dissociation rate. We show now that MA-5 and MA-20 are potent antagonists of the negative cooperativity induced by insulin, and reverse the insulin-induced acceleration whether added simultaneously with insulin or after insulin. The reversal of the insulin-induced acceleration is almost immediate. These data strengthen the concept therefore that the insulin-receptor complex has access to alternative conformational states that can be stabilized by ligand-induced site-site interactions.
与其他单克隆抗体不同，两种针对胰岛素受体的单克隆抗体MA - 5和MA - 20不会模拟胰岛素对125I - 胰岛素从受体上解离的加速作用（负协同效应）。相反，MA - 5和MA - 20显著减慢了解离速率。我们现在表明，MA - 5和MA - 20是胰岛素诱导的负协同效应的有效拮抗剂，并且无论与胰岛素同时添加还是在胰岛素之后添加，都能逆转胰岛素诱导的加速作用。胰岛素诱导的加速作用的逆转几乎是即时的。因此，这些数据强化了这样一种概念，即胰岛素 - 受体复合物能够进入可通过配体诱导的位点 - 位点相互作用而稳定的替代构象状态。
