Monoclonal antibodies to the human insulin receptor mimic a spectrum of biological effects in transfected 3T3/HIR fibroblasts without activating receptor kinase

The effects of four monoclonal antibodies to the alpha subunit of the human insulin receptor were studied in transfected mouse 3T3 fibroblasts expressing human insulin receptors (3T3/HIR). Three antibodies, MA-5, MA-20, and MA-51, mimicked insulin stimulation of the uptake of both 2-deoxy-D-glucose and alpha-aminoisobutyrio acid, and S6 kinase activity. Antibody MA-5 also mimicked insulin stimulation of 3H]thymidine incorporation and cell growth. Although these antibodies mimicked insulin stimulation of biological effects, they failed to significantly activate insulin receptor tyrosine kinase activity. These studies suggest, therefore, that the insulin receptor can signal a variety of cellular functions without stimulation of receptor kinase activity.