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 receptors have been characterized in hepatocytes and Kupffer cells isolated from adult rat liver, Affinity labeling with [I-125]insulin-like growth factor II revealed a protein of M(r) 250 000 in both cell types, Labeling was inhibited by an antiserum against the mannose 6-phosphate/insulin-like growth factor II receptor, In Kupffer cells, [I-125]insulin-like growth factor II was also cross-linked to a second protein of M(r) 130 000, In both cell types, insulin-like growth factor II was 10 times more potent than insulin-like growth factor I in displacing [I-125]insulin-like growth factor II from its receptor, The mannose 6-phosphate-specific uptake of [I-125]arylsulfatase A via the mannose 6-phosphate/insulin-like growth factor II receptor was inhibited by insulin-like growth factor II and antibodies against the receptor, but was not affected by insulin-like growth factor I, insulin or transforming growth factor beta 1. Cell surface iodination followed by immunoprecipitation of the mannose 6-phosphate/insulin-like growth factor II receptor showed that expression 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 insulin-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 hepatocytes and Kupffer cells.