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Updated: May 16, 2026

Radiolabeling and Quantification of Cellular Levels of Phosphoinositides by High Performance Liquid Chromatography-coupled Flow Scintillation
Published on: January 6, 2016
Phosphatidylinositol 4-kinase IIα function at endosomes is regulated by the ubiquitin ligase Itch
Julia Mössinger1, Marnix Wieffer, Eberhard Krause
1Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustraße 6, 14195 Berlin, Germany.
Abstract:
Phosphatidylinositol (PI) 4-phosphate (PI(4)P) and its metabolizing enzymes serve important functions in cell signalling and membrane traffic. PI 4-kinase type IIα (PI4KIIα) regulates Wnt signalling, endosomal sorting of signalling receptors, and promotes adaptor protein recruitment to endosomes and the trans-Golgi network. Here we identify the E3 ubiquitin ligase Itch as binding partner and regulator of PI4KIIα function. Itch directly associates with and ubiquitinates PI4KIIα, and both proteins colocalize on endosomes containing Wnt-activated frizzled 4 (Fz4) receptor. Depletion of PI4KIIα or Itch regulates Wnt signalling with corresponding changes in Fz4 internalization and degradative sorting. These findings unravel a new molecular link between phosphoinositide-regulated endosomal membrane traffic, ubiquitin and the modulation of Wnt signalling.
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