Abstract
Phosphatidylinositol-4,5-bisphosphate (PIP(2)) is known to play an important role in signal transduction and membrane trafficking. We show that one enzyme responsible for PIP(2) production, phosphatidylinositol-4-phosphate 5-kinase type 1beta (PIPKbeta), is essential for epidermal growth factor receptor (EGFR)-mediated endocytosis. Expression of murine PIPKbeta in NR6 cells expressing EGFR strikingly increased receptor internalization. Moreover, the kinase was shown to form an immunoprecipitable complex with EGFR. Expression of either a truncated kinase or a kinase dead mutant inhibited EGFR endocytosis and also blocked the membrane recruitment of PIPKbeta and both clathrin light chain and dynamin. Our results delineate a novel mechanism by which PIPKbeta regulates receptor-mediated endocytosis and receptor tyrosine kinase membrane traffic.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Blotting, Western
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Cell Line
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Cell Membrane / metabolism
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Clathrin / chemistry
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Clathrin / metabolism
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Cloning, Molecular
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Dynamins
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Electrophoresis, Polyacrylamide Gel
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Endocytosis*
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Epidermal Growth Factor / metabolism*
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GTP Phosphohydrolases / chemistry
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GTP Phosphohydrolases / metabolism
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Mice
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Microscopy, Confocal
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Microscopy, Fluorescence
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Mutation
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Phosphotransferases (Alcohol Group Acceptor) / chemistry
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Phosphotransferases (Alcohol Group Acceptor) / genetics*
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Phosphotransferases (Alcohol Group Acceptor) / metabolism*
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Precipitin Tests
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Protein Binding
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Protein Isoforms
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Receptor Protein-Tyrosine Kinases / metabolism
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Sindbis Virus / genetics
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Time Factors
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Transfection
Substances
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Clathrin
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Protein Isoforms
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Epidermal Growth Factor
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Phosphotransferases (Alcohol Group Acceptor)
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1-phosphatidylinositol-4-phosphate 5-kinase
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Receptor Protein-Tyrosine Kinases
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GTP Phosphohydrolases
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Dynamins