AAK1 explained

Adaptor-associated protein kinase 1 also known as AP2-associated protein kinase 1 is an enzyme that in humans is encoded by the AAK1 gene^{[1] [2] [3]} and is involved in clathrin mediated endocytosis. Alternatively spliced transcript variants have been described, but their biological validity has not been determined.^[3]

Function

Adaptor-related protein complex 2 (AP-2 complexes) functions during receptor-mediated endocytosis to trigger clathrin assembly, interact with membrane-bound receptors, and recruit endocytic accessory factors. This gene encodes a member of the SNF1 subfamily of Ser/Thr protein kinases. The protein interacts with and phosphorylates a subunit of the AP-2 complex, which promotes binding of AP-2 to sorting signals found in membrane-bound receptors and subsequent receptor endocytosis. Its kinase activity is stimulated by clathrin.^[3]

Further reading

• Kikuno R, Nagase T, Ishikawa K, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O . Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro . DNA Research . 6 . 3 . 197–205 . Jun 1999 . 10470851 . 10.1093/dnares/6.3.197 . free .
• Ricotta D, Conner SD, Schmid SL, von Figura K, Honing S . Phosphorylation of the AP2 mu subunit by AAK1 mediates high affinity binding to membrane protein sorting signals . The Journal of Cell Biology . 156 . 5 . 791–5 . Mar 2002 . 11877457 . 2173304 . 10.1083/jcb.200111068 .
• Conner SD, Schmid SL . Differential requirements for AP-2 in clathrin-mediated endocytosis . The Journal of Cell Biology . 162 . 5 . 773–9 . Sep 2003 . 12952931 . 2172816 . 10.1083/jcb.200304069 .
• Conner SD, Schröter T, Schmid SL . AAK1-mediated micro2 phosphorylation is stimulated by assembled clathrin . Traffic . 4 . 12 . 885–90 . Dec 2003 . 14617351 . 10.1046/j.1398-9219.2003.0142.x . 84066885 . free .
• Mishra SK, Hawryluk MJ, Brett TJ, Keyel PA, Dupin AL, Jha A, Heuser JE, Fremont DH, Traub LM . Dual engagement regulation of protein interactions with the AP-2 adaptor alpha appendage . The Journal of Biological Chemistry . 279 . 44 . 46191–203 . Oct 2004 . 15292237 . 10.1074/jbc.M408095200 . free .
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP . Large-scale characterization of HeLa cell nuclear phosphoproteins . Proceedings of the National Academy of Sciences of the United States of America . 101 . 33 . 12130–5 . Aug 2004 . 15302935 . 514446 . 10.1073/pnas.0404720101 . 2004PNAS..10112130B . free .
• Kim JE, Tannenbaum SR, White FM . Global phosphoproteome of HT-29 human colon adenocarcinoma cells . Journal of Proteome Research . 4 . 4 . 1339–46 . 2005 . 16083285 . 10.1021/pr050048h .
• Collawn JF . Unlocking the mysteries of Na+-K+-ATPase endocytosis: phosphorylation is the key . American Journal of Respiratory Cell and Molecular Biology . 35 . 1 . 1–2 . Jul 2006 . 16782842 . 2658690 . 10.1165/rcmb.f317 .
• Schmid EM, Ford MG, Burtey A, Praefcke GJ, Peak-Chew SY, Mills IG, Benmerah A, McMahon HT . Role of the AP2 beta-appendage hub in recruiting partners for clathrin-coated vesicle assembly . PLOS Biology . 4 . 9 . e262 . Sep 2006 . 16903783 . 1540706 . 10.1371/journal.pbio.0040262 . free .
• Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP . A probability-based approach for high-throughput protein phosphorylation analysis and site localization . Nature Biotechnology . 24 . 10 . 1285–92 . Oct 2006 . 16964243 . 10.1038/nbt1240 . 14294292 .
• Takahashi T, Furuchi T, Naganuma A . Endocytic Ark/Prk kinases play a critical role in adriamycin resistance in both yeast and mammalian cells . Cancer Research . 66 . 24 . 11932–7 . Dec 2006 . 17178891 . 10.1158/0008-5472.CAN-06-3220 . free .
• Henderson DM, Conner SD . A novel AAK1 splice variant functions at multiple steps of the endocytic pathway . Molecular Biology of the Cell . 18 . 7 . 2698–706 . Jul 2007 . 17494869 . 1924820 . 10.1091/mbc.E06-09-0831 .

Notes and References

1. Conner SD, Schmid SL . Identification of an adaptor-associated kinase, AAK1, as a regulator of clathrin-mediated endocytosis . The Journal of Cell Biology . 156 . 5 . 921–9 . Mar 2002 . 11877461 . 2173317 . 10.1083/jcb.200108123 .
2. Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S . The protein kinase complement of the human genome . Science . 298 . 5600 . 1912–34 . Dec 2002 . 12471243 . 10.1126/science.1075762 . 2002Sci...298.1912M . 26554314 .
3. Web site: Entrez Gene: AAK1 AP2 associated kinase 1.