{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T03:27:03Z","timestamp":1776137223725,"version":"3.50.1"},"reference-count":18,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,3,4]]},"abstract":"<jats:p>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 \u03bc2 subunit and to clathrin via the \u03b2 subunit. Here we show that binding of AP2 to sorting signals in vitro is regulated by phosphorylation of the \u03bc2 subunit of AP2. Phosphorylation of \u03bc2 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 \u03b1 or \u03b22 subunit, suggesting that phosphorylation of \u03bc2 is critical for regulation of AP2 binding to sorting signals. Phosphorylation of \u03bc2 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 \u03bc2 subunit by AAK1 ensures high affinity binding of AP2 to sorting signals of cargo membrane proteins during the initial steps of receptor-mediated endocytosis.<\/jats:p>","DOI":"10.1083\/jcb.200111068","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:46:23Z","timestamp":1027701983000},"page":"791-795","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":241,"title":["Phosphorylation of the AP2 \u03bc subunit by AAK1 mediates high affinity binding to membrane protein sorting signals"],"prefix":"10.1083","volume":"156","author":[{"given":"Doris","family":"Ricotta","sequence":"first","affiliation":[{"name":"1Institute for Biochemistry II, University of Go\u0308ttingen, 37073 Go\u0308ttingen, Germany"}]},{"given":"Sean D.","family":"Conner","sequence":"additional","affiliation":[{"name":"2The Scripps Research Institute, La Jolla, CA 92037"}]},{"given":"Sandra L.","family":"Schmid","sequence":"additional","affiliation":[{"name":"2The Scripps Research Institute, La Jolla, CA 92037"}]},{"given":"Kurt","family":"von Figura","sequence":"additional","affiliation":[{"name":"1Institute for Biochemistry II, University of Go\u0308ttingen, 37073 Go\u0308ttingen, Germany"}]},{"given":"Stefan","family":"Ho\u0308ning","sequence":"additional","affiliation":[{"name":"1Institute for Biochemistry II, University of Go\u0308ttingen, 37073 Go\u0308ttingen, Germany"}]}],"member":"291","published-online":{"date-parts":[[2002,3,4]]},"reference":[{"key":"2023072213223970800_BIB1","doi-asserted-by":"crossref","first-page":"27160","DOI":"10.1074\/jbc.272.43.27160","volume":"272","year":"1997","journal-title":"J. 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