[Effect of wortmannin on endocytosis of epidermal growth factor receptors].
Using subcellular fractionation of human carcinoma A431 cells in Percoll gradient it was shown that P13-kinase (P13-K) inhibitor wortmannin blocked the transition of the EGF-receptor complexes from the early to the late endosomes. Under conditions when the receptor TK-dependent sorting system is mainly involved, i.e. at low EGF concentrations, the efficiency of sorting was seen to fall 5-10-folls in the presence of wortmannin compared to the control. At high EGF concentrations of the toxin inhibitory effect was no more than 30%. Immunofluorescent analysis has demonstrated that wortmannin treatment led to a juxtranuclear localization of EGF-receptors, which is presumably characteristic of the late endosomes. However, this localization became obvious even in 15 min following endocytosis stimulation, when EGF-receptors, according to the Percoll data, were associated mainly with the early endosomes. A possible role of phosphatidylinositol metabolism products in endocytosis regulation is discussed in addition to the structural and functional organization of the early endosomal compartments. A conclusion is made that P13-K may be a component of the EGF receptor-specific sorting system.
Zheleznova
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Institute of Cytology RAS, St. Petersburg. zheleznova@hotmail.com
Nikol'skiĭ
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NN
Kornilova
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ES
D000730:Androstadienes / Q000494:pharmacology*; D004705:Endocytosis / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D000081082:Phosphoinositide-3 Kinase Inhibitors; D014407:Tumor Cells, Cultured; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D066246:ErbB Receptors; D000077191:Wortmannin