Stimulation of tyrosine-specific phosphorylation in vitro by insulin-like growth factor I.

Several mitogens elicit tyrosine-specific protein kinase activities. Although the physiological significance of this is unclear, the generality of these reactions implies that this may be an inherent feature of growth factor-growth factor receptor interactions. The observed mitogenic properties of the polypeptide insulin-like growth factor I (IGF-I) indicated that it might also stimulate such activity. We report here that IGF-I stimulates a tyrosine-specific protein kinase in a time- and dose-dependent fashion. The close correspondence between an approximate 50% effective dose (ED50) of phosphorylation and an approximate Kd for IGF-I binding leads us to conclude that a high-affinity IGF-I receptor, not the structurally similar insulin receptor, is the mediator of IGF-I stimulated kinase activity. Immunoprecipitation indicates that both the beta-subunit of the IGF-I receptor and the beta-subunit of the insulin receptor are targets for the IGF-I-stimulated protein kinase.