DOI: 10.1083/jcb.200111068. Phosphorylation of the AP2 μ subunit by AAK1 mediates high affinity binding to membrane protein sorting signals

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

10.1083/jcb.200111068

Crossref journal-article

Rockefeller University Press

The Journal of Cell Biology (291)

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.

Bibliography

Ricotta, D., Conner, S. D., Schmid, S. L., von Figura, K., & HoÌning, S. (2002). Phosphorylation of the AP2 Î¼ subunit by AAK1 mediates high affinity binding to membrane protein sorting signals. The Journal of Cell Biology, 156(5), 791â795.

Authors 5

Doris Ricotta (first)
Sean D. Conner (additional)
Sandra L. Schmid (additional)
Kurt von Figura (additional)
Stefan Höning (additional)

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Dates

Type	When
Created	23 years ago (July 26, 2002, 12:46 p.m.)
Deposited	2 years, 1 month ago (July 22, 2023, 9:22 a.m.)
Indexed	4 days, 18 hours ago (Aug. 21, 2025, 1:45 p.m.)
Issued	23 years, 5 months ago (March 4, 2002)
Published	23 years, 5 months ago (March 4, 2002)
Published Online	23 years, 5 months ago (March 4, 2002)
Published Print	23 years, 5 months ago (March 4, 2002)

Funders 0

None

BibTeX

@article{Ricotta_2002, title={Phosphorylation of the AP2 μ subunit by AAK1 mediates high affinity binding to membrane protein sorting signals}, volume={156}, ISSN={0021-9525}, url={http://dx.doi.org/10.1083/jcb.200111068}, DOI={10.1083/jcb.200111068}, number={5}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Ricotta, Doris and Conner, Sean D. and Schmid, Sandra L. and von Figura, Kurt and Höning, Stefan}, year={2002}, month=mar, pages={791–795} }

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