The Insulin-Like Growth Factor-II/Mannose 6-Phosphate Receptor
Competitive binding experiments first demonstrated that insulin-like growth factor (IGF) receptors are distinct from insulin receptors and that there are two IGF receptors based on relative preference for IGF-I, IGF-II, and insulin1. The IGF-I receptor or type I IGF receptor binds IGF-I with higher affinity than IGF-II, and binds insulin with much lower affinity than IGF-II. The IGF-II receptor or type II IGF receptor binds IGF-II with considerably higher affinity than IGF-I and does not bind insulin at all. The structures of these two IGF receptors were defined by affinity crosslinking, biosynthetic labeling, purification, and finally, molecular cloning2–5. The IGF-I receptor is very similar to the insulin receptor, consisting of two alpha subunits of 130 kDa, and two beta subunits of 95 kDa. The beta subunit has intrinsic tyrosine kinase activity which is activated by autophosphorylation following ligand binding to the alpha subunit. The structure of the IGF-II receptor is quite different from the structure of the IGF-I receptor. The IGF-II receptor is a single 250 kDa glycoprotein which lacks tyrosine kinase activity.
KeywordsTyrosine Cysteine Electrophoresis Serine Polyacrylamide
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