期刊
JOURNAL OF CELL SCIENCE
卷 119, 期 3, 页码 571-580出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.02752
关键词
type II phosphatidylinositol 4-kinase; endocytosis; degradation; epidermal growth factor
类别
资金
- Medical Research Council [G117/554, G117/554(71630)] Funding Source: Medline
- Medical Research Council [G117/554] Funding Source: researchfish
- MRC [G117/554] Funding Source: UKRI
The type II alpha isoform of phosphatidylinositol 4-kinase has recently been shown to function in the recruitment of adaptor protein-1 complexes to the trans-Golgi network. Here we show that phosphatidylinositol 4-kinase II alpha is also a component of highly dynamic membranes of the endosomal system where it colocalises with protein markers of the late endosome and with endocytosed epidermal growth factor. When phosphatidylinositol 4-kinase II alpha activity was inhibited in vivo using the monoclonal antibody 4C5G or by depression of endogenous phosphatidylinositol 4-kinase II alpha protein levels using RNA interference, ligand-bound epidermal growth factor receptor failed to traffic to late endosomes and instead accumulated in vesicles in a sub-plasma membrane compartment. Furthermore, lysosomal degradation of activated epidermal growth factor receptor was dramatically impaired in small inhibitory RNA-treated cells. We demonstrate that phosphatidylinositol 4-kinase Hot is necessary for the correct endocytic traffic and downregulation of activated epidermal growth factor receptor.
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