Evidence that receptor aggregation may play a role in transmembrane signaling through the insulin-like growth factor-I receptor.
alpha IR-3 is a mouse monoclonal antibody that binds to an epitope on the human insulin-like growth factor I (IGF-I) receptor and inhibits [125I]IGF-I binding to this receptor on human skin fibroblasts (HSF) and Hep G2 human hepatoblastoma cells. Unlike the natural ligand (IGF-I), neither intact alpha IR-3 nor its monovalent Fab fragment stimulate aminoisobutyric acid (AIB) uptake in HSF, and both competitively antagonize IGF-I's ability to produce this effect. However, when HSF are incubated with alpha IR-3 or its Fab' fragment, subsequent exposure to anti-mouse immunoglobulin G (IgG) produces a potent stimulation of AIB uptake. Anti-Mouse IgG by itself does not effect AIB uptake. alpha IR-3 also antagonizes IGF-I's ability to stimulate glycogen synthesis in Hep G2 cells. As with AIB uptake in HSF, the combination of alpha IR-3 followed by anti-mouse IgG stimulates glycogen synthesis in Hep G2 cells to the same extent as that produced by IGF-I. The triggering of these two biological effects depends on the concentration of both alpha IR-3 and anti-mouse IgG. These results are consistent with the possibility that local aggregation or cross-linking of IGF-I receptors plays an important role in transmembrane signaling by this receptor.
Ikari
N
N
Charles A. Dana Research Institute, Boston, Massachusetts.
Yoshino
H
H
Moses
A C
AC
Flier
J S
JS
D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal; D002460:Cell Line; D000939:Epitopes / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D051379:Mice; D011972:Receptor, Insulin / Q000502:physiology*; D017451:Receptors, Somatomedin; D015398:Signal Transduction
D000621:Aminoisobutyric Acids; D000911:Antibodies, Monoclonal; D000939:Epitopes; D007074:Immunoglobulin G; D017451:Receptors, Somatomedin; C100049:2-aminoisobutyric acid; D011972:Receptor, Insulin