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 [125I]insulin-like growth factor II revealed a protein of Mr 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, [125I]insulin-like growth factor II was also cross-linked to a second protein of Mr 130,000. In both cell types, insulin-like growth factor II was 10 times more potent than insulin-like growth factor I in displacing [125I]insulin-like growth factor II from its receptor. The mannose 6-phosphate-specific uptake of [125I]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.
Schmitz
F
F
Department of Medicine, Georg-August-Universität, Göttingen, Germany.
Bresciani
R
R
Hartmann
H
H
Braulke
T
T
D000818:Animals; D001345:Autoradiography; D002478:Cells, Cultured / Q000187:drug effects; D002553:Cerebroside-Sulfatase / Q000187:drug effects* / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D007728:Kupffer Cells / Q000187:drug effects* / Q000201:enzymology; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008360:Mannosephosphates / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017527:Receptor, IGF Type 2 / Q000187:drug effects*
D008360:Mannosephosphates; D017527:Receptor, IGF Type 2; C027693:mannose-6-phosphate; D007335:Insulin-Like Growth Factor II; D002553:Cerebroside-Sulfatase