Gene Symbol: AAK1
Description: AP2 associated kinase 1
Alias: AP2-associated protein kinase 1, adaptor-associated kinase 1
Species: human
Products:     AAK1

Top Publications

  1. Henderson D, Conner S. A novel AAK1 splice variant functions at multiple steps of the endocytic pathway. Mol Biol Cell. 2007;18:2698-706 pubmed
    Phosphorylation is a critical step in regulating receptor transport through the endocytic pathway. AAK1 is a serine/threonine kinase that is thought to coordinate the recruitment of AP-2 to receptors containing tyrosine-based ..
  2. Conner S, Schmid S. Identification of an adaptor-associated kinase, AAK1, as a regulator of clathrin-mediated endocytosis. J Cell Biol. 2002;156:921-9 pubmed
    ..We find that AAK1 copurifies with adaptor protein (AP)2 and that it directly binds the ear domain of alpha-adaptin in vivo and in ..
  3. Ricotta D, Conner S, Schmid S, von Figura K, Honing S. Phosphorylation of the AP2 mu subunit by AAK1 mediates high affinity binding to membrane protein sorting signals. J Cell Biol. 2002;156:791-5 pubmed
    ..2 occurs at a single threonine residue (Thr-156) and is mediated by the newly discovered adaptor-associated kinase, AAK1, which copurifies with AP2...
  4. Mishra S, Hawryluk M, Brett T, Keyel P, Dupin A, Jha A, et al. Dual engagement regulation of protein interactions with the AP-2 adaptor alpha appendage. J Biol Chem. 2004;279:46191-203 pubmed
    ..that the WXX(F/W)X(D/E) interaction motif found in several endocytic proteins, including synaptojanin 1, stonin 2, AAK1, GAK, and NECAP1, binds a second interaction site on the bilobal alpha appendage, located on the N-terminal beta ..
  5. Rao S, Gurbani D, Du G, Everley R, Browne C, Chaikuad A, et al. Leveraging Compound Promiscuity to Identify Targetable Cysteines within the Kinome. Cell Chem Biol. 2019;: pubmed publisher
    ..identified 23 kinases that are amenable to covalent inhibition including MKNK2, MAP2K1/2/3/4/6/7, GAK, AAK1, BMP2K, MAP3K7, MAPKAPK5, GSK3A/B, MAPK1/3, SRC, YES1, FGFR1, ZAK (MLTK), MAP3K1, LIMK1, and RSK2...
  6. Shehata S, Deak M, Collodet C, Spiegl S, Geley S, Sumpton D, et al. Identification of novel PCTAIRE-1/CDK16 substrates using a chemical genetic screen. Cell Signal. 2019;59:53-61 pubmed publisher
    ..Our screen has identified potential PCTAIRE-1 substrates (AP2-Associated Kinase 1 (AAK1), dynamin 1, and synaptojanin 1) in brain that have been shown to regulate crucial steps of receptor endocytosis, ..
  7. Loi M, Ligeon L, MUNZ C. MHC Class I Internalization via Autophagy Proteins. Methods Mol Biol. 2019;1880:455-477 pubmed publisher
    ..seems to result from defective internalization of MHC class I molecules dependent on adaptor protein kinase 1 (AAK1), involved in clathrin-mediated endocytosis...
  8. Agajanian M, Walker M, Axtman A, Ruela de Sousa R, Serafin D, Rabinowitz A, et al. WNT Activates the AAK1 Kinase to Promote Clathrin-Mediated Endocytosis of LRP6 and Establish a Negative Feedback Loop. Cell Rep. 2019;26:79-93.e8 pubmed publisher
    ..Here, using a gain-of-function screen of the human kinome, we report that the AP2 associated kinase 1 (AAK1), a known CME enhancer, inhibits WNT signaling...
  9. Kaye A, Cornett E, Hart B, Patil S, Pham A, Spalitta M, et al. Novel Pharmacological Nonopioid Therapies in Chronic Pain. Curr Pain Headache Rep. 2018;22:31 pubmed publisher
    ..bisphosphonates, antibodies, sodium channel blockers, NMDA antagonists, TRP receptors, transdermal vitamin D, AAK1 kinase inhibition, calcitonin gene-related peptide (CGRP), TRPV4 antagonists, cholecystokinin, delta opioid ..

More Information


  1. Pu S, Xiao F, Schor S, Bekerman E, Zanini F, Barouch Bentov R, et al. Feasibility and biological rationale of repurposing sunitinib and erlotinib for dengue treatment. Antiviral Res. 2018;155:67-75 pubmed publisher
    ..We reported that the cellular kinases AAK1 and GAK regulate intracellular trafficking of multiple viruses and that sunitinib and erlotinib, approved ..
  2. Shi B, Conner S, Liu J. Dysfunction of endocytic kinase AAK1 in ALS. Int J Mol Sci. 2014;15:22918-32 pubmed publisher
    ..Using the yeast two-hybrid system, we identified the adaptor-associated kinase 1 (AAK1), a regulatory protein in clathrin-coated vesicle endocytic pathway that selectively interacted with the mutant but ..
  3. Fu X, Ke M, Yu W, Wang X, Xiao Q, Gu M, et al. Periodic Variation of AAK1 in an Aβ1-42-Induced Mouse Model of Alzheimer's Disease. J Mol Neurosci. 2018;65:179-189 pubmed publisher
    ..Adaptor-associated kinase 1 (AAK1), which binds to the adaptor protein complex 2 (AP-2), regulates the process of clathrin-mediated endocytosis...
  4. So J, Pasculescu A, Dai A, Williton K, James A, Nguyen V, et al. Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy. Sci Signal. 2015;8:rs3 pubmed publisher
    ..were classified as resistors were PX domain-containing serine/threonine kinase (PXK) and AP2-associated kinase 1 (AAK1), which promote receptor endocytosis and may enable cells to resist TRAIL-induced apoptosis by enhancing ..
  5. Leger H, Santana E, Leu N, Smith E, Beltran W, Aguirre G, et al. Ndr kinases regulate retinal interneuron proliferation and homeostasis. Sci Rep. 2018;8:12544 pubmed publisher
    ..Consistent with the latter, Ndr deletion dramatically reduced levels of Aak1, an Ndr substrate that regulates vesicle trafficking...
  6. Bekerman E, Neveu G, Shulla A, Brannan J, Pu S, Wang S, et al. Anticancer kinase inhibitors impair intracellular viral trafficking and exert broad-spectrum antiviral effects. J Clin Invest. 2017;127:1338-1352 pubmed publisher
    ..We previously reported that AAK1 and GAK, kinase regulators of the host adaptor proteins AP1 and AP2, are essential for hepatitis C virus (HCV) ..
  7. Xiao F, Wang S, Barouch Bentov R, Neveu G, Pu S, Beer M, et al. Interactions between the Hepatitis C Virus Nonstructural 2 Protein and Host Adaptor Proteins 1 and 4 Orchestrate Virus Release. MBio. 2018;9: pubmed publisher
    ..We demonstrated that the host kinases AAK1 and GAK regulate HCV infection by controlling these clathrin-associated APs...
  8. Louis J, Lu Y, Pieschl R, Tian Y, Hong Y, Dandapani K, et al. [3H]BMT-046091 a potent and selective radioligand to determine AAK1 distribution and target engagement. Neuropharmacology. 2017;118:167-174 pubmed publisher
    Adaptor-associated kinase 1 (AAK1), a member of the Ark1/Prk1 family of serine/threonine kinases, plays a role in modulating clatherin coated endocytosis of specific surface receptors...
  9. Loi M, Muller A, Steinbach K, Niven J, Barreira da Silva R, Paul P, et al. Macroautophagy Proteins Control MHC Class I Levels on Dendritic Cells and Shape Anti-viral CD8(+) T Cell Responses. Cell Rep. 2016;15:1076-1087 pubmed publisher
    ..Internalization of MHC class I molecules occurs less efficiently if AAK1 cannot be recruited via Atg8/LC3B...
  10. Jang J, Wang X, VEDELL P, Wen J, Zhang J, Ellison D, et al. Custom Gene Capture and Next-Generation Sequencing to Resolve Discordant ALK Status by FISH and IHC in Lung Adenocarcinoma. J Thorac Oncol. 2016;11:1891-1900 pubmed publisher
    ..tissue, we identified EML4-baculoviral AIP repeat containing 6 gene (BIRC6) and AP2 associated kinase 1 gene (AAK1)-ALK fusion genes...
  11. Collawn J. Unlocking the mysteries of Na+-K+-ATPase endocytosis: phosphorylation is the key. Am J Respir Cell Mol Biol. 2006;35:1-2 pubmed
  12. Manna P, Obado S, Boehm C, Gadelha C, Sali A, Chait B, et al. Lineage-specific proteins essential for endocytosis in trypanosomes. J Cell Sci. 2017;130:1379-1392 pubmed publisher
    ..brucei (Tb)EpsinR, several endosomal SNAREs plus orthologues of SMAP and the AP-2 associated kinase AAK1 as interacting with clathrin...
  13. Neveu G, Ziv Av A, Barouch Bentov R, Berkerman E, Mulholland J, Einav S. AP-2-associated protein kinase 1 and cyclin G-associated kinase regulate hepatitis C virus entry and are potential drug targets. J Virol. 2015;89:4387-404 pubmed publisher
    Hepatitis C virus (HCV) enters its target cell via clathrin-mediated endocytosis. AP-2-associated protein kinase 1 (AAK1) and cyclin G-associated kinase (GAK) are host kinases that regulate clathrin adaptor protein (AP)-mediated ..
  14. Malinowski J, Denny J, Bielinski S, Basford M, Bradford Y, Peissig P, et al. Genetic variants associated with serum thyroid stimulating hormone (TSH) levels in European Americans and African Americans from the eMERGE Network. PLoS ONE. 2014;9:e111301 pubmed publisher
    ..These results support the previously reported association between PDE8B and serum TSH levels in European Americans and emphasize the need for additional genetic studies in more diverse populations. ..
  15. Conner S, Schmid S. Differential requirements for AP-2 in clathrin-mediated endocytosis. J Cell Biol. 2003;162:773-9 pubmed
    ..Adaptor-associated kinase (AAK1), an AP-2 binding partner, modulates AP-2 function by phosphorylating its mu2 subunit...
  16. Manning G, Whyte D, Martinez R, Hunter T, Sudarsanam S. The protein kinase complement of the human genome. Science. 2002;298:1912-34 pubmed
    ..We also identified 106 protein kinase pseudogenes. Chromosomal mapping revealed several small clusters of kinase genes and revealed that 244 kinases map to disease loci or cancer amplicons. ..
  17. Sorrell F, Szklarz M, Abdul Azeez K, Elkins J, Knapp S. Family-wide Structural Analysis of Human Numb-Associated Protein Kinases. Structure. 2016;24:401-11 pubmed publisher
    ..Here we report the first high-resolution structures of kinases AAK1 and BIKE in complex with two drug candidates...
  18. Gupta Rossi N, Ortica S, Meas Yedid V, Heuss S, Moretti J, Olivo Marin J, et al. The adaptor-associated kinase 1, AAK1, is a positive regulator of the Notch pathway. J Biol Chem. 2011;286:18720-30 pubmed publisher
    ..We show here that AAK1, the adaptor-associated kinase 1, directly interacts with the membrane-tethered active form of Notch released by ..
  19. Latourelle J, Pankratz N, Dumitriu A, Wilk J, Goldwurm S, Pezzoli G, et al. Genomewide association study for onset age in Parkinson disease. BMC Med Genet. 2009;10:98 pubmed publisher
    ..7 x 10(-6)) which lies in an intron of the AAK1 gene...
  20. Takahashi T, Furuchi T, Naganuma A. Endocytic Ark/Prk kinases play a critical role in adriamycin resistance in both yeast and mammalian cells. Cancer Res. 2006;66:11932-7 pubmed
    ..We also found that HEK293 cells that overexpressed AAK1, a member of the human Ark/Prk family, were Adriamycin resistant...
  21. Conner S, Schröter T, Schmid S. AAK1-mediated micro2 phosphorylation is stimulated by assembled clathrin. Traffic. 2003;4:885-90 pubmed
    b>AAK1, the adaptor-associated kinase 1, phosphorylates the micro2 subunit of AP2 and regulates the recruitment of AP2 to tyrosine-based internalization motifs found on membrane-bound receptors...
  22. Kostich W, Hamman B, Li Y, Naidu S, Dandapani K, Feng J, et al. Inhibition of AAK1 Kinase as a Novel Therapeutic Approach to Treat Neuropathic Pain. J Pharmacol Exp Ther. 2016;358:371-86 pubmed publisher
    ..One of the lines from this screen, which contained a null allele of the adapter protein-2 associated kinase 1 (AAK1) gene, had a normal response in acute pain assays (hot plate, phase I formalin), but a markedly reduced response to ..
  23. Sorensen E, Conner S. AAK1 regulates Numb function at an early step in clathrin-mediated endocytosis. Traffic. 2008;9:1791-800 pubmed publisher
    ..In this study, we show that Numb binds to and is phosphorylated by adaptor-associated kinase 1 (AAK1), a key endocytic kinase...
  24. Schmid E, Ford M, Burtey A, Praefcke G, Peak Chew S, Mills I, et al. Role of the AP2 beta-appendage hub in recruiting partners for clathrin-coated vesicle assembly. PLoS Biol. 2006;4:e262 pubmed
    ..However, proteins such as beta-arrestin (non-visual arrestin) and autosomal recessive hypercholesterolemia protein, which have direct clathrin interactions, will remain in the coated pits with their interacting receptors...