Binding and degradation of insulin-like growth factors I and II by rat kidney membrane.

We have investigated the binding and degradation of insulin-like growth factors (IGF)/somatomedin by rat kidney membrane using 125I-labeled IGF-I and IGF-II. The binding of IGF-I and IGF-II were specific to their respective kidney membrane receptors with indicated Mr of 130,000 and 250,000, respectively. The IGF-I and IGF-II degrading activities of the kidney membrane were also found to be specific for the respective hormones. Comparison of the binding and degrading kinetics suggested the two systems to be separate. The characterization of the degrading activities revealed the activities to be neutral sulfhydryl proteases which are different from insulin neutral protease. Identity of these proteases as separate from the insulin protease was revealed from the specificity of the degrading enzymes for IGF and the differential inhibitory effect of N-ethylmaleimide on the enzymes compared to insulin protease. In summary, the IGF binding and degrading activities of kidney membrane are two independent systems with specificity for IGF-I or IGF-II, respectively. Additionally, the characterized IGF-degrading systems revealed the enzymes to be different from the previously described insulin protease.