title: Reversal of insulin-induced negative cooperativity by monoclonal antibodies that stabilize the slowly dissociating ("Ksuper") state of the insulin receptor.
abstract: 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.
authors.affiliation: Department of Diabetes, Endocrinology and Metabolism, City of Hope National Medical Center, Duarte, CA 91010.
authors.forename: J L
authors.initials: JL
authors.lastname: Gu
authors.forename: I D
authors.initials: ID
authors.lastname: Goldfine
authors.forename: J R
authors.initials: JR
authors.lastname: Forsayeth
authors.forename: P
authors.initials: P
authors.lastname: De Meyts
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D002478:Cells, Cultured; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism*; D008954:Models, Biological; D011485:Protein Binding; D011972:Receptor, Insulin / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D007328:Insulin; D011972:Receptor, Insulin