Open AccessMonoclonal antibodies to the human insulin receptor that activate glucose transport but not insulin receptor kinase activity.
Author(s) -
John Forsayeth,
F. José,
Madhur K. Sinha,
Betty A. Maddux,
Ira D. Goldfine
Publication year - 1987
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.84.10.3448
Subject(s) - autophosphorylation , insulin receptor , irs2 , insulin receptor substrate , insulin , insulin like growth factor 1 receptor , grb10 , receptor , monoclonal antibody , biology , medicine , endocrinology , antibody , biochemistry , phosphorylation , insulin resistance , protein kinase a , immunology , growth factor
Three mouse monoclonal antibodies were produced that reacted with the alpha subunit of the human insulin receptor. All three both immunoprecipitated 125I-labeled insulin receptors from IM-9 lymphocytes and competitively inhibited 125I-labeled insulin binding to its receptor. Unlike insulin, the antibodies failed to stimulate receptor autophosphorylation in both intact IM-9 lymphocytes and purified human placental insulin receptors. Moreover, unlike insulin, the antibodies failed to stimulate receptor-mediated phosphorylation of exogenous substrates. However, like insulin, two of the three antibodies stimulated glucose transport in isolated human adipocytes. One antibody, on a molar basis, was as potent as insulin. These studies indicate, therefore, that monoclonal antibodies to the insulin receptor can mimic a major function of insulin without activating receptor kinase activity. They also raise the possibility that certain actions of insulin such as stimulation of glucose transport may not require the activation of receptor kinase activity.