Phosphorylation of the AP2 μ subunit by AAK1 mediates high affinity binding to membrane protein sorting signals

Doris Ricotta, Sean D. Conner, Sandra L. Schmid, Kurt Von Figura, Stefan Höning

Research output: Contribution to journalArticle

169 Citations (Scopus)

Abstract

During receptor-mediated endocytosis, AP2 complexes act as a bridge between the cargo membrane proteins and the clathrin coat by binding to sorting signals via the μ2 subunit and to clathrin via the β subunit. Here we show that binding of AP2 to sorting signals in vitro is regulated by phosphorylation of the μ2 subunit of AP2. Phosphorylation of μ2 enhances the binding affinity of AP2 for sorting motifs as much as 25-fold compared with dephosphorylated AP2. The recognition of sorting signals was not affected by the phosphorylation status of the α or β2 subunit, suggesting that phosphorylation of μ2 is critical for regulation of AP2 binding to sorting signals. Phosphorylation of μ2 occurs at a single threonine residue (Thr-156) and is mediated by the newly discovered adaptor-associated kinase, AAK1, which copurifies with AP2. We propose that phosphorylation of the AP2 μ2 subunit by AAK1 ensures high affinity binding of AP2 to sorting signals of cargo membrane proteins during the initial steps of receptor-mediated endocytosis.

Original languageEnglish (US)
Pages (from-to)791-795
Number of pages5
JournalJournal of Cell Biology
Volume156
Issue number5
DOIs
StatePublished - Mar 4 2002

Fingerprint

Protein Sorting Signals
Membrane Proteins
Phosphorylation
Clathrin
Endocytosis
Threonine
Phosphotransferases

Keywords

  • Clathrin
  • Coated vesicle
  • Endocytosis
  • Receptor
  • Trafficking

ASJC Scopus subject areas

  • Cell Biology

Cite this

Phosphorylation of the AP2 μ subunit by AAK1 mediates high affinity binding to membrane protein sorting signals. / Ricotta, Doris; Conner, Sean D.; Schmid, Sandra L.; Von Figura, Kurt; Höning, Stefan.

In: Journal of Cell Biology, Vol. 156, No. 5, 04.03.2002, p. 791-795.

Research output: Contribution to journalArticle

Ricotta, Doris ; Conner, Sean D. ; Schmid, Sandra L. ; Von Figura, Kurt ; Höning, Stefan. / Phosphorylation of the AP2 μ subunit by AAK1 mediates high affinity binding to membrane protein sorting signals. In: Journal of Cell Biology. 2002 ; Vol. 156, No. 5. pp. 791-795.
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