Inhibition of IGF II-induced redistribution of mannose 6-phosphate receptors by the phosphatidylinositol 3-kinase inhibitor, wortmannin.
The effects of wortmannin, a selective inhibitor of phosphatidylinositol (PI)3-kinase on insulin-like growth factor II (IGF II)-induced redistribution of the 300 kDa mannose 6-phosphate/IGF II receptor (MPR 300) has been studied in human hepatoma HepG2 cells. IGF II increased the expression of MPR 300 at the cell surface threefold that was completely abolished by wortmannin at 100-300 nM. Higher concentrations of wortmannin also reduced the basal MPR 300-dependent uptake of ligands to 68% of controls. Neither the transport of two lysosomal enzymes nor the secretion of the IGF binding protein-1 were affected by wortmannin. These results show that activation of PI3-kinase plays a critical role in the IGF II-stimulated redistribution of MPR 300 initiated rather by IGF II binding to tyrosine kinase receptors than to the MPR 300.
Körner
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Institute of Biochemistry II, University of Göttingen, Germany.
Braulke
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D000730:Androstadienes / Q000494:pharmacology*; D002402:Cathepsin D / Q000378:metabolism; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008024:Ligands; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D017527:Receptor, IGF Type 2 / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D000077191:Wortmannin; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D000730:Androstadienes; D004791:Enzyme Inhibitors; D018970:Insulin-Like Growth Factor Binding Protein 1; D008024:Ligands; D017527:Receptor, IGF Type 2; D007335:Insulin-Like Growth Factor II; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D020794:Receptor Protein-Tyrosine Kinases; D001619:beta-N-Acetylhexosaminidases; D002402:Cathepsin D; D000077191:Wortmannin