Stimulation of phosphatidylinositol kinase type I-mediated phosphatidylinositol (4,5)-bisphosphate synthesis by AP-2mu-cargo complexes

Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):11934-9. doi: 10.1073/pnas.0510306103. Epub 2006 Jul 31.

Abstract

Phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P(2)] is an important factor for a variety of cellular functions ranging from cell signaling to actin cytoskeletal dynamics and endocytic membrane traffic. Here, we have identified the clathrin adaptor complex AP-2 as a regulator of phosphatidylinositol 4-phosphate 5-kinase (PIPK)-mediated PI(4,5)P(2) synthesis. AP-2 directly interacts with the kinase core domain of type I PIPK isozymes via its mu2-subunit in vitro and in native protein extracts. Endocytic cargo protein binding to mu2 leads to a potent stimulation of PIPK activity. These data thus identify a positive feedback loop consisting of endocytic cargo proteins, AP-2mu, and PIPK type I which may provide a specific pool of PI(4,5)P(2) dedicated to clathrin/AP-2-dependent receptor internalization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Protein Complex 2 / chemistry*
  • Adaptor Protein Complex mu Subunits / chemistry*
  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Cytoskeleton / metabolism
  • Feedback, Physiological
  • Fibroblasts / metabolism
  • HeLa Cells
  • Humans
  • Phosphatidylinositol 4,5-Diphosphate / chemistry*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Protein Binding
  • Protein Isoforms
  • Transcription Factor AP-2 / metabolism*

Substances

  • Adaptor Protein Complex 2
  • Adaptor Protein Complex mu Subunits
  • Phosphatidylinositol 4,5-Diphosphate
  • Protein Isoforms
  • Transcription Factor AP-2
  • adaptor protein complex 2, mu 1 subunit
  • Phosphotransferases (Alcohol Group Acceptor)
  • 1-phosphatidylinositol-4-phosphate 5-kinase