Phosphatidylinositol-4-phosphate 5-kinase-1beta is essential for epidermal growth factor receptor-mediated endocytosis

J Biol Chem. 2001 Dec 14;276(50):47212-6. doi: 10.1074/jbc.C100490200. Epub 2001 Oct 1.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line
  • Cell Membrane / metabolism
  • Clathrin / chemistry
  • Clathrin / metabolism
  • Cloning, Molecular
  • Dynamins
  • Electrophoresis, Polyacrylamide Gel
  • Endocytosis*
  • Epidermal Growth Factor / metabolism*
  • GTP Phosphohydrolases / chemistry
  • GTP Phosphohydrolases / metabolism
  • Mice
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Mutation
  • Phosphotransferases (Alcohol Group Acceptor) / chemistry
  • Phosphotransferases (Alcohol Group Acceptor) / genetics*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Precipitin Tests
  • Protein Binding
  • Protein Isoforms
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Sindbis Virus / genetics
  • Time Factors
  • Transfection

Substances

  • Clathrin
  • Protein Isoforms
  • Epidermal Growth Factor
  • Phosphotransferases (Alcohol Group Acceptor)
  • 1-phosphatidylinositol-4-phosphate 5-kinase
  • Receptor Protein-Tyrosine Kinases
  • GTP Phosphohydrolases
  • Dynamins