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.