Interaction between heterologous receptor tyrosine kinases. Hormone-stimulated insulin receptors activate unoccupied IGF-I receptors.
To determine whether heterologous receptor tyrosine kinases interact with each other we have investigated the ability of insulin receptors to transphosphorylate and transactivate IGF-I receptors. Using partially purified receptors we show that hormone-stimulated insulin receptors induced a 40% increase in IGF-I receptor phosphorylation. Remarkably, this transphosphorylation of IGF-I receptors by insulin receptors resulted in a 2.5-fold augmentation of the IGF-I receptor tyrosine kinase activity for substrates. Our findings demonstrate that transphosphorylation with transactivation can occur between insulin and IGF-I receptors. We would like to propose that such a phenomenon participates in the insulin-induced pleiotropic program by mediating the growth promoting effects of the hormone.
Tartare
S
S
Institut National de la Santé et de la Recherche Médicale, INSERM U145, Faculté de Médecine, Nice, France.
Ballotti
R
R
Van Obberghen
E
E
D016475:3T3 Cells; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004789:Enzyme Activation; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011972:Receptor, Insulin / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D017451:Receptors, Somatomedin; D014162:Transfection
D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I; D000255:Adenosine Triphosphate; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin