INSULIN-INDUCED SURFACE REDISTRIBUTION REGULATES INTERNALIZATION OF THE INSULIN-RECEPTOR AND REQUIRES ITS AUTOPHOSPHORYLATION

The role of insulin-induced receptor autophosphorylation in its internalization was analyzed by comparing I-125-labeled insulin (I-125-insulin) internalization in Chinese hamster ovary (CHO) cell lines transfected with normal (CHO.T) or mutated insulin receptors. In four cell lines with a defect of insulin-induced autophosphorylation, I-125-insulin internalization was impaired. By contrast, in CHO.T cells and in two other CHO cell lines with amino acid deletions or insertions that do not perturb autophosphorylation, I-125-insulin internalization was not affected. A morphological analysis showed that the inhibition is linked to the ligand-specific surface redistribution in which the insulin-receptor complexes leave microvilli and concentrate on nonvillous segments of the membrane where endocytosis occurs.