Effect of insulin-like growth factor II on uptake of arylsulfatase A by cultured rat hepatocytes and Kupffer cells.

Mannose 6-phosphate/insulin-like growth factor II re- ceptors have been characterized in hepatocytes and Kupffer cells isolated from adult rat liver. Affinity labeling with [‘2511insulin-like growth factor II re- vealed a protein of M, 250 000 in both cell types. Labeling was inhibited by an antiserum against the mannose 6-phosphate/insulin-like growth factor II re- ceptor. In Kupffer cells, [‘251]insulin-like growth fac- tor II was also cross-linked to a second protein of M, 130 000. In both cell types, insulin-like growth factor II was 10 times more potent than insulin-like growth factor I in displacing [1251]insulin-likegrowth factor II from its receptor. The mannose bphosphate-specific uptake of (12SI]arylsulfatase A via the mannose 6- phosphate/insulin-like growth factor II receptor was inhibited by insulin-like growth factor II and anti- bodies against the receptor, but was not affected by insulin-like growth factor I, insulin or transforming growth factor #lI.Cell surface iodination followed by immunoprecipitation of the mannose fGphosphate/in- sulin-like growth factor II receptor showed that ex- pression of the mannose 6-phosphate/insulin-like growth factor II receptors at the plasma membrane was increased two-fold by insulin-like growth factor II. These results suggest that binding of insuliu-like growth factor II to the mannose 6_phosphate/insulin- like growth factor II receptor blocks the binding and uptake of mannose 6-phosphate-containing lysosomal enzymes and may be directly involved in a co-ordinate regulation of ligand uptake from plasma into hepato- cytes and Kupffer cells. Key words: Endocytosis, rat hepatocytes, Kupffer cells; Insulin-like growth factor II; Lysosomal en- zyme; Mannose 6-phosphate/insulin-like growth fac- tor II receptor.