9qb5

Structural highlights

Function

AAK1_HUMAN Regulates clathrin-mediated endocytosis by phosphorylating the AP2M1/mu2 subunit of the adaptor protein complex 2 (AP-2) which ensures high affinity binding of AP-2 to cargo membrane proteins during the initial stages of endocytosis. Isoform 1 and isoform 2 display similar levels of kinase activity towards AP2M1. Regulates phosphorylation of other AP-2 subunits as well as AP-2 localization and AP-2-mediated internalization of ligand complexes. Phosphorylates NUMB and regulates its cellular localization, promoting NUMB localization to endosomes. Binds to and stabilizes the activated form of NOTCH1, increases its localization in endosomes and regulates its transcriptional activity.^{[1] [2] [3] [4]}

References

1. ↑ Conner SD, Schmid SL. Differential requirements for AP-2 in clathrin-mediated endocytosis. J Cell Biol. 2003 Sep 1;162(5):773-9. PMID:12952931 doi:http://dx.doi.org/10.1083/jcb.200304069
2. ↑ Henderson DM, Conner SD. A novel AAK1 splice variant functions at multiple steps of the endocytic pathway. Mol Biol Cell. 2007 Jul;18(7):2698-706. Epub 2007 May 9. PMID:17494869 doi:http://dx.doi.org/10.1091/mbc.E06-09-0831
3. ↑ Sorensen EB, Conner SD. AAK1 regulates Numb function at an early step in clathrin-mediated endocytosis. Traffic. 2008 Sep;9(10):1791-800. doi: 10.1111/j.1600-0854.2008.00790.x. Epub, 2008 Jul 24. PMID:18657069 doi:http://dx.doi.org/10.1111/j.1600-0854.2008.00790.x
4. ↑ Gupta-Rossi N, Ortica S, Meas-Yedid V, Heuss S, Moretti J, Olivo-Marin JC, Israel A. The adaptor-associated kinase 1, AAK1, is a positive regulator of the Notch pathway. J Biol Chem. 2011 May 27;286(21):18720-30. doi: 10.1074/jbc.M110.190769. Epub, 2011 Apr 4. PMID:21464124 doi:http://dx.doi.org/10.1074/jbc.M110.190769