Affinage

AAK1

AP2-associated protein kinase 1 · UniProt Q2M2I8

Length
961 aa
Mass
103.9 kDa
Annotated
2026-06-09
37 papers in source corpus 19 papers cited in narrative 19 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AAK1 is a Prk/Ark-family serine/threonine kinase that couples the assembly of clathrin coats to cargo selection during clathrin-mediated endocytosis (PMID:11877461). It constitutively associates with the AP2 adaptor complex through the alpha-adaptin ear domain and phosphorylates the AP2 mu2 subunit (AP2M1) at Thr-156, a modification that increases AP2 affinity for tyrosine-based sorting signals up to 25-fold to drive cargo recognition (PMID:11877461, PMID:11877457); assembled clathrin cages stimulate this kinase activity, so AAK1 reads coat assembly as the trigger for cargo capture (PMID:14617351). Through this activity AAK1 controls the internalization and trafficking of multiple receptors, including the transferrin receptor (PMID:11877461, PMID:17494869), LRP6—where AP2M1-dependent endocytosis forms a transcription-uncoupled negative feedback loop on WNT/beta-catenin signaling (PMID:30605688)—ErbB4 (PMID:21802010), Notch (PMID:21464124), and transferrin receptor 1, whose endocytosis raises cellular iron to promote ferroptosis (PMID:41407700). AAK1 additionally phosphorylates the endocytic accessory protein Numb at Thr-102 to govern its membrane distribution and cargo-selective internalization (PMID:18657069). AAK1 activity is set by upstream kinases: NDR1/2 phosphorylate AAK1 in neurons to regulate dendrite growth (PMID:22445341), and PKCβII activates AAK1 during ferroptosis (PMID:41407700). Beyond endocytosis, AAK1 directly phosphorylates the focal adhesion proteins PDLIM5 and Talin1, is recruited to focal adhesions via a C-terminal PDZ-binding motif, and promotes their timely release during adhesion disassembly to accelerate cell migration (PMID:42082516). AAK1 has been genetically and pharmacologically implicated in persistent pain through a spinal, alpha-2 adrenergic-dependent mechanism (PMID:27411717), in NF-κB-driven inflammatory injury (PMID:36733250), and in caspase-11 non-canonical inflammasome activation via LPS internalization (PMID:35982051).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2002 High

    Established AAK1 as the physiological AP2 mu2 kinase and linked it directly to clathrin-coated pit function, defining its core molecular role in endocytosis.

    Evidence Co-purification with AP2, in vivo/in vitro binding to alpha-adaptin ear, in vitro kinase assay on mu2, and transferrin internalization assays

    PMID:11877457 PMID:11877461

    Open questions at the time
    • Did not resolve how clathrin assembly couples to kinase activation
    • Structural basis of AAK1-AP2 association not defined
  2. 2002 High

    Mapped the functional consequence of mu2 phosphorylation, showing Thr-156 phosphorylation increases AP2 affinity for sorting signals up to 25-fold, mechanistically connecting AAK1 activity to cargo recognition.

    Evidence In vitro phosphorylation with Thr-156 site mutagenesis and quantitative AP2-sorting signal binding assays

    PMID:11877457

    Open questions at the time
    • In vitro affinity gain not directly tied to cargo loading rates in cells
    • Reversal/phosphatase that turns the signal off not identified
  3. 2003 High

    Showed that assembled clathrin, not just adaptor binding, activates AAK1, establishing clathrin as a regulatory activator coupling coat assembly to cargo selection.

    Evidence In vitro kinase assays comparing clathrin cages vs triskelia plus AAK1 domain mapping to clathrin heavy and light chains

    PMID:14617351

    Open questions at the time
    • Conformational mechanism of activation unresolved
    • Quantitative thresholds in vivo unknown
  4. 2007 Medium

    Extended AAK1 function beyond uptake to endosomal recycling and identified a long splice variant with a second clathrin-binding domain, indicating action at multiple trafficking steps.

    Evidence Pulldown binding assays, RNAi knockdown, transferrin recycling and CBD2 overexpression assays

    PMID:17494869

    Open questions at the time
    • Kinase-dependence of recycling role not separated
    • Single-lab functional readouts
  5. 2008 High

    Identified Numb as a non-AP2 AAK1 substrate (Thr-102), broadening the kinase's regulation of endocytic accessory machinery in a cargo-selective manner.

    Evidence Co-IP, in vitro kinase assay, T102A mutant, RNAi, and cargo-specific internalization assays

    PMID:18657069

    Open questions at the time
    • How Numb phosphorylation selects transferrin/LDL over EGF cargo not mechanistically resolved
  6. 2011 Medium

    Connected AAK1 to receptor signaling outputs by showing it regulates Notch trafficking and ErbB4 levels, implicating endocytic control in developmental and neurotrophic signaling.

    Evidence Co-IP, overexpression/depletion, Rab5 colocalization and Notch reporter assays; chemical proteomics plus RNAi for ErbB4

    PMID:21464124 PMID:21802010

    Open questions at the time
    • Direct phosphorylation of Notch or ErbB4 by AAK1 not demonstrated
    • Kinase-dependence of adaptor role for Notch unclear
  7. 2012 High

    Placed AAK1 downstream of NDR1/2 kinases in neurons, establishing an upstream regulatory input and a role in dendrite growth.

    Evidence Analog-sensitive NDR1/2 chemical genetics with thiophosphate labeling and mass spectrometry, plus neuronal morphology assays

    PMID:22445341

    Open questions at the time
    • AAK1 phosphosite(s) by NDR1/2 not mapped
    • Functional link between phosphorylation and endocytic activity not defined
  8. 2016 High

    Demonstrated an in vivo physiological role in persistent pain, localizing AAK1 action to the spinal cord and placing it upstream of alpha-2 adrenergic signaling.

    Evidence Knockout mice, selective and non-brain-penetrant inhibitors, behavioral pain models, receptor antagonist epistasis, spinal electrophysiology

    PMID:27411717

    Open questions at the time
    • Molecular substrate underlying the antinociceptive effect not identified
    • Connection to endocytic mechanism unresolved
  9. 2019 High

    Defined a transcription-uncoupled WNT negative feedback loop in which AAK1 drives AP2M1-dependent LRP6 endocytosis, linking the core endocytic mechanism to a signaling output.

    Evidence Kinome screen, siRNA and inhibitor, WNT time-course, AP2M1 phosphorylation, and LRP6 internalization assays

    PMID:30605688

    Open questions at the time
    • How WNT signaling activates AAK1 not defined
    • Direct LRP6-AP2 cargo selection step not biochemically isolated
  10. 2022 Medium

    Implicated AAK1 in NF-κB-driven inflammation through control of IκBα stability and identified miR-671-5p as a post-transcriptional regulator.

    Evidence miRNA target validation, IκBα stability assays, NF-κB reporters, and LPS-injury mouse models

    PMID:36733250

    Open questions at the time
    • Mechanistic link between AAK1 kinase activity and IκBα stability unclear
    • Direct substrate not identified
  11. 2023 Medium

    Showed AAK1 promotes LPS internalization required for caspase-11 non-canonical inflammasome activation, extending its endocytic role to innate immune sensing.

    Evidence Chemical target engagement and genetic epistasis across multiple knockout lines (Casp11, Casp1, Msr1, Nlrp3) in sepsis models

    PMID:35982051

    Open questions at the time
    • Specific endocytic cargo/route for LPS uptake not fully defined
    • Role of AAK1 catalytic activity not isolated
  12. 2024 Medium

    Demonstrated AAK1 drives viral entry by phosphorylating AP2M1 at Thr-156 to enable ACE2-AP2M1 coupling, reusing the canonical cargo-selection mechanism for SARS-CoV-2 endocytosis.

    Evidence AAK1 inhibitor treatment, Thr-156 phosphorylation assays, AP2M1-ACE2 Co-IP, pseudovirus infection assays

    PMID:38377825

    Open questions at the time
    • Whether ACE2 is a direct AP2 sorting cargo not structurally resolved
    • Single-lab antiviral validation
  13. 2024 Medium

    Revealed a kinase-independent function via the C. elegans orthologue SEL-5, which acts with retromer to positively regulate Wnt signaling without requiring AP2M1 phosphorylation, distinguishing catalytic from scaffolding roles.

    Evidence Genetic epistasis with retromer mutants, kinase-dead alleles, and migration/outgrowth assays in C. elegans

    PMID:39028260

    Open questions at the time
    • Mammalian relevance of the kinase-independent retromer role untested
    • Molecular basis of the SEL-5/retromer cooperation unknown
  14. 2025 High

    Identified PKCβII as an upstream activating kinase that wires AAK1 into a PKCβII-AAK1-AP2M1 pathway driving TFR1 endocytosis, iron uptake, and ferroptosis with tumor-suppressive consequences.

    Evidence Kinase identification and phosphorylation assays, Co-IP, TFR1 endocytosis and iron measurements, phospho-mutant analysis, and tumor xenograft models

    PMID:41407700

    Open questions at the time
    • AAK1 activating phosphosite(s) targeted by PKCβII not detailed here
    • Generality across ferroptosis contexts unknown
  15. 2026 High

    Established a CME-independent role at focal adhesions, where AAK1 directly phosphorylates PDLIM5 and Talin1 to time adhesion disassembly and accelerate migration.

    Evidence Phosphoproteomic and motif-guided substrate identification, biochemical kinase assays, PDZ-binding-motif pulldowns, live-cell focal adhesion imaging, and phospho-mutant migration assays

    PMID:42082516

    Open questions at the time
    • Upstream signal recruiting AAK1 to adhesions not identified
    • Relationship between adhesion and endocytic pools of AAK1 unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How AAK1 is selectively partitioned between its endocytic cargo-selection role and its CME-independent functions (focal adhesions, kinase-independent retromer signaling), and what governs context-specific upstream activation, remains unresolved.
  • No unified model linking the multiple upstream activators to distinct downstream substrate pools
  • Structural basis of substrate and clathrin recognition not solved
  • Direct mammalian validation of kinase-independent functions lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016740 transferase activity 4 GO:0060090 molecular adaptor activity 1
Localization
GO:0005768 endosome 2 GO:0005886 plasma membrane 2 GO:0031410 cytoplasmic vesicle 2 GO:0005856 cytoskeleton 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 5 R-HSA-162582 Signal Transduction 2 R-HSA-168256 Immune System 2 R-HSA-5357801 Programmed Cell Death 2
Partners
AP2A1AP2M1CLTCLRP6NOTCH1NUMBPDLIM5TLN1

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 AAK1 is a serine/threonine kinase of the Prk/Ark family that directly binds the ear domain of alpha-adaptin of the AP2 complex in vivo and in vitro, copurifies with AP2, colocalizes with clathrin and AP2 in clathrin-coated pits, and specifically phosphorylates the mu2 (AP2M1) subunit in vitro, resulting in decreased AP2-stimulated transferrin internalization. Co-purification, in vivo and in vitro binding assays, in vitro kinase assay, stage-specific endocytosis assays, immunofluorescence colocalization The Journal of cell biology High 11877461
2002 AAK1 phosphorylates mu2 (AP2M1) at a single threonine residue (Thr-156), and this phosphorylation enhances the binding affinity of AP2 for tyrosine-based sorting motifs up to 25-fold compared to dephosphorylated AP2, thereby promoting cargo recognition during receptor-mediated endocytosis. In vitro phosphorylation assays, site-specific mutagenesis (Thr-156), affinity binding assays measuring AP2-sorting signal interaction The Journal of cell biology High 11877457
2003 Assembled clathrin stimulates AAK1-mediated mu2 phosphorylation; clathrin cages provide greater stimulation than unassembled clathrin triskelia. Efficient stimulation involves multiple interactions between several AAK1 domains and both heavy and light chains of clathrin, indicating clathrin plays a regulatory (not merely structural) role by activating AAK1 within coated pits. In vitro kinase assays with assembled clathrin cages vs. triskelia, domain-mapping binding assays Traffic (Copenhagen, Denmark) High 14617351
2007 A long splice variant of AAK1 (AAK1L) contains an additional C-terminal clathrin-binding domain (CBD2) with multiple low-affinity interaction motifs that directly binds clathrin. Overexpression of CBD2 impairs transferrin endocytosis. Additionally, AAK1 depletion by RNAi or CBD2 overexpression impairs transferrin recycling from early/sorting endosomes, indicating AAK1 functions at multiple steps of the endosomal pathway. Protein interaction studies (pulldown), in vitro kinase assays, RNAi knockdown, transferrin recycling assays, overexpression studies Molecular biology of the cell Medium 17494869
2008 AAK1 binds to and phosphorylates Numb at Thr-102. AAK1 overexpression redistributes Numb to perinuclear endosomes, while AAK1 depletion causes Numb accumulation at the plasma membrane. A phosphorylation-null Numb mutant (T102A) disrupts transferrin and LDL internalization but not EGF uptake, and accumulates at the plasma membrane with elevated colocalization with coated pit markers. Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis (T102A), RNAi knockdown, internalization assays, immunofluorescence colocalization Traffic (Copenhagen, Denmark) High 18657069
2011 AAK1 directly interacts with the membrane-tethered active form of Notch (released by metalloprotease cleavage). Active AAK1 stabilizes both the membrane-tethered activated Notch and its monoubiquitinated form upstream of gamma-secretase cleavage. AAK1 acts as an adaptor for Notch interaction with CME components such as Eps15b. AAK1 overexpression increases localization of activated Notch to Rab5-positive endocytic vesicles; AAK1 depletion interferes with this localization. Co-immunoprecipitation, overexpression and depletion studies, immunofluorescence colocalization with Rab5-positive vesicles, Notch signaling reporter assays The Journal of biological chemistry Medium 21464124
2011 AAK1 is identified as a relevant target of the natural product K252a; loss of AAK1 (via RNAi) alters ErbB4 receptor trafficking and expression levels, revealing a previously unrecognized role for AAK1 in Nrg1/ErbB4-mediated neurotrophic factor signaling. Chemical genomics (differentially active analogs + SILAC-based affinity enrichment proteomics), RNAi knockdown, ErbB4 trafficking and expression assays Chemistry & biology Medium 21802010
2012 NDR1/2 kinases phosphorylate AAK1 in the brain as identified by chemical genetics (analog-sensitive kinase alleles with thiophosphate labeling). AAK1 functions downstream of NDR1/2 and contributes to dendrite growth regulation in mammalian pyramidal neurons. Chemical genetics (analog-sensitive NDR1/2 kinase alleles, thiophosphate labeling, mass spectrometry substrate identification), dominant-negative and constitutively active NDR1/2 mutants, siRNA knockdown, in vivo and in vitro neuronal morphology assays Neuron High 22445341
2014 AAK1 selectively interacts with mutant (but not wild-type) SOD1 in ALS models, as identified by yeast two-hybrid. In transgenic SOD1-ALS rodent models, AAK1 is mislocated from normal endosomal/presynaptic compartments into aggregates containing mutant SOD1 and neurofilament proteins, and AAK1 protein levels are decreased in ALS patients. Yeast two-hybrid, immunofluorescence colocalization in transgenic ALS mouse and rat models, protein level quantification International journal of molecular sciences Low 25514244
2016 AAK1 knockout mice have normal responses in acute pain assays but markedly reduced responses to persistent pain (phase II formalin) and fail to develop tactile allodynia after spinal nerve ligation. AAK1 inhibitors act in the spinal cord (demonstrated by non-brain-penetrant inhibitor and local spinal administration) and their antinociceptive mechanism requires alpha-2 adrenergic receptor signaling (blocked by alpha-2 receptor antagonists but not opioid receptor antagonists). Genetic knockout, pharmacological inhibition with selective inhibitors, non-brain-penetrant inhibitor studies, local administration, behavioral pain assays (formalin, SNL, CCI, diabetic neuropathy), in vivo spinal cord electrophysiology The Journal of pharmacology and experimental therapeutics High 27411717
2019 AAK1 promotes clathrin-mediated endocytosis of LRP6 to suppress WNT/beta-catenin signaling. WNT treatment drives AAK1-dependent phosphorylation of AP2M1, clathrin-coated pit maturation, and endocytosis of LRP6 in a transcription-uncoupled negative feedback loop. Reciprocally, AAK1 genetic silencing or pharmacological inhibition activates WNT signaling. Gain-of-function kinome screen, genetic silencing (siRNA), pharmacological inhibition, time-course WNT treatment assays, AP2M1 phosphorylation assays, LRP6 plasma membrane localization and internalization assays Cell reports High 30605688
2022 AAK1 positively regulates NF-κB signaling by controlling the stability of the inhibitory protein IκBα; miR-671-5p directly targets AAK1 mRNA for post-transcriptional degradation, reducing AAK1 activity and thereby dampening NF-κB-dependent pulmonary inflammatory injury. miRNA target validation, protein stability assays for IκBα, NF-κB reporter/signaling assays, AAK1 overexpression/knockdown in cell and mouse LPS-injury models Molecular therapy : the journal of the American Society of Gene Therapy Medium 36733250
2023 AAK1 promotes LPS internalization required for caspase-11 activation (non-canonical inflammasome/pyroptosis pathway) in macrophages. PHZ-OH targets AAK1 and prevents AAK1-mediated LPS internalization for caspase-11 activation. In vivo, AAK1 inhibitor-treated mice are protected similarly to Casp11-/- and Msr1-/- mice, but not to Casp1/11-/- or Nlrp3-/- mice. Chemical screening, physical and physiological target engagement studies, gene-modified mice (Casp11-/-, Casp1-/-, Casp1/11-/-, Msr1-/-, Nlrp3-/-), in vivo sepsis models, LPS internalization assays Cell death & disease Medium 35982051
2023 AAK1 binding to Notch promotes the differentiation of neural stem cells (NSCs) into neurons rather than astrocytes in the context of ischemic brain injury; miR-124 delivered via M2 microglia extracellular vesicles suppresses AAK1 expression to modulate this pathway. Proteomic analysis of NSC samples, miR-124 knockdown in extracellular vesicles, in vivo MCAO mouse model, NSC differentiation assays Stroke Low 37586072
2024 AAK1 promotes SARS-CoV-2 endocytosis by phosphorylating AP2M1 at Thr-156, which facilitates the direct interaction between AP2M1 and ACE2 for clathrin-mediated endocytosis of the virus; AAK1 inhibition disrupts this interaction and blocks viral entry. AAK1 inhibitor treatment, AP2M1 phosphorylation assays (Thr-156), co-immunoprecipitation of AP2M1 and ACE2, SARS-CoV-2 pseudovirus infection assays in hACE2-HEK293 cells European journal of medicinal chemistry Medium 38377825
2024 In C. elegans, SEL-5 (the AAK1 orthologue) acts together with the retromer complex as a positive regulator of EGL-20/Wnt signaling during QL neuroblast daughter cell migration and excretory canal cell outgrowth. Importantly, SEL-5 kinase activity is not required for these roles, and neither process depends on DPY-23/AP2M1 phosphorylation, revealing a kinase-independent function. Genetic epistasis (double mutants with retromer complex), kinase-dead mutant analysis, cell migration and outgrowth assays in C. elegans, Wnt pathway reporter assays eLife Medium 39028260
2025 PKCβII phosphorylates and activates AAK1 during ferroptosis, forming a PKCβII–AAK1–AP2M1 pathway. Activated AAK1 phosphorylates AP2M1, which facilitates clathrin recruitment to mediate transferrin receptor 1 (TFR1) endocytosis, increasing cellular total iron and ferrous iron to promote ferroptosis. A non-phosphorylatable AAK1 mutation inhibits ferroptosis and promotes breast tumor growth in vivo. Kinase identification assays, phosphorylation assays, Co-IP, clathrin recruitment assays, TFR1 endocytosis assays, iron measurement, ferroptosis assays, phospho-mimetic/phospho-null AAK1 mutants, in vivo tumor xenograft models Nature communications High 41407700
2026 AAK1 directly phosphorylates PDLIM5 and Talin1 (identified via motif-guided in silico, biochemical, and phosphoproteomic screens). AAK1 is recruited to focal adhesions and its activity peaks at the onset of focal adhesion disassembly. The conserved AAK1 C-terminal PDZ-binding motif mediates direct low-affinity binding to PDLIM5. Phospho-mimetic and phospho-null mutant analyses support that AAK1-dependent phosphorylation promotes timely release of PDLIM5 and Talin1 during focal adhesion disassembly to accelerate cell migration. Phosphoproteomic screen, biochemical kinase assays, live-cell imaging (focal adhesion dynamics), pulldown/binding assays (PDZ-binding motif), phospho-mimetic and phospho-null mutant analysis, cell migration assays Nature communications High 42082516
2025 BIN1 (isoform 1) and AAK1 are proximal/interacting proteins in mouse brain neurons, identified by TurboID-based proximity labeling and validated by immunostaining and proximity ligation assays. TurboID proximity labeling, label-free quantitative proteomics, immunostaining, proximity ligation assay bioRxivpreprint Low bio_10.1101_2025.03.09.642169

Source papers

Stage 0 corpus · 37 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Identification of an adaptor-associated kinase, AAK1, as a regulator of clathrin-mediated endocytosis. The Journal of cell biology 268 11877461
2002 Phosphorylation of the AP2 mu subunit by AAK1 mediates high affinity binding to membrane protein sorting signals. The Journal of cell biology 231 11877457
2012 Chemical genetic identification of NDR1/2 kinase substrates AAK1 and Rabin8 Uncovers their roles in dendrite arborization and spine development. Neuron 116 22445341
2016 Inhibition of AAK1 Kinase as a Novel Therapeutic Approach to Treat Neuropathic Pain. The Journal of pharmacology and experimental therapeutics 71 27411717
2019 WNT Activates the AAK1 Kinase to Promote Clathrin-Mediated Endocytosis of LRP6 and Establish a Negative Feedback Loop. Cell reports 68 30605688
2003 AAK1-mediated micro2 phosphorylation is stimulated by assembled clathrin. Traffic (Copenhagen, Denmark) 61 14617351
2008 AAK1 regulates Numb function at an early step in clathrin-mediated endocytosis. Traffic (Copenhagen, Denmark) 59 18657069
2023 M2 Microglia Extracellular Vesicle miR-124 Regulates Neural Stem Cell Differentiation in Ischemic Stroke via AAK1/NOTCH. Stroke 49 37586072
2007 A novel AAK1 splice variant functions at multiple steps of the endocytic pathway. Molecular biology of the cell 47 17494869
2011 The adaptor-associated kinase 1, AAK1, is a positive regulator of the Notch pathway. The Journal of biological chemistry 43 21464124
2023 Extracellular vesicle-transmitted miR-671-5p alleviates lung inflammation and injury by regulating the AAK1/NF-κB axis. Molecular therapy : the journal of the American Society of Gene Therapy 34 36733250
2014 Dysfunction of endocytic kinase AAK1 in ALS. International journal of molecular sciences 33 25514244
2011 AAK1 identified as an inhibitor of neuregulin-1/ErbB4-dependent neurotrophic factor signaling using integrative chemical genomics and proteomics. Chemistry & biology 33 21802010
2022 Discovery and Optimization of Biaryl Alkyl Ethers as a Novel Class of Highly Selective, CNS-Penetrable, and Orally Active Adaptor Protein-2-Associated Kinase 1 (AAK1) Inhibitors for the Potential Treatment of Neuropathic Pain. Journal of medicinal chemistry 17 35261239
2023 Recent progress in discovery of novel AAK1 inhibitors: from pain therapy to potential anti-viral agents. Journal of enzyme inhibition and medicinal chemistry 15 37955299
2021 Discovery, Structure-Activity Relationships, and In Vivo Evaluation of Novel Aryl Amides as Brain Penetrant Adaptor Protein 2-Associated Kinase 1 (AAK1) Inhibitors for the Treatment of Neuropathic Pain. Journal of medicinal chemistry 14 34270254
2018 Periodic Variation of AAK1 in an Aβ1-42-Induced Mouse Model of Alzheimer's Disease. Journal of molecular neuroscience : MN 14 29774516
2022 miRNA-384-3p alleviates sevoflurane-induced nerve injury by inhibiting Aak1 kinase in neonatal rats. Brain and behavior 12 35726359
2021 A patent review of adaptor associated kinase 1 (AAK1) inhibitors (2013-present). Expert opinion on therapeutic patents 11 33971786
2022 Novel 1-hydroxy phenothiazinium-based derivative protects against bacterial sepsis by inhibiting AAK1-mediated LPS internalization and caspase-11 signaling. Cell death & disease 9 35982051
2024 Design, synthesis, and biological evaluation of novel AAK1/HDACs dual inhibitors against SARS-CoV-2 entry. Bioorganic chemistry 7 39581172
2023 Evaluating the ability of some natural phenolic acids to target the main protease and AAK1 in SARS COV-2. Scientific reports 7 37147518
2022 Quadruple Target Evaluation of Diversity-Optimized Halogen-Enriched Fragments (HEFLibs) Reveals Substantial Ligand Efficiency for AP2-Associated Protein Kinase 1 (AAK1). Frontiers in chemistry 7 35186897
2017 [3H]BMT-046091 a potent and selective radioligand to determine AAK1 distribution and target engagement. Neuropharmacology 7 28315351
2022 lncRNA ZFAS1 promotes intervertebral disc degeneration by upregulating AAK1. Open medicine (Warsaw, Poland) 6 36561842
2024 Caenorhabditis elegans SEL-5/AAK1 regulates cell migration and cell outgrowth independently of its kinase activity. eLife 4 39028260
2024 Synthesis of 3-heteroaryl-pyrrolo[2,3-b]pyridines as potent inhibitors of AP-2-associated protein kinase 1 (AAK1) with antiviral activity. European journal of medicinal chemistry 4 39427517
2025 Development of pyrazolo[1,5-a]pyrimidine based macrocyclic kinase inhibitors targeting AAK1. European journal of medicinal chemistry 3 40882436
2024 Design, synthesis and biological evaluation of novel 1,2,4a,5-tetrahydro-4H-benzo[b][1,4]oxazino[4,3-d][1,4]oxazine-based AAK1 inhibitors with anti-viral property against SARS-CoV-2. European journal of medicinal chemistry 3 38377825
2024 Development of a novel AAK1 inhibitor via Kinobeads-based screening. Scientific reports 3 38509168
2025 Identification of aberrant plasma vesicles containing AAK1 and CCDC18-AS1 in adolescents with major depressive disorder and preliminary exploration of treatment efficacy. Genomics 1 39798887
2025 AAK1 activation-mediated iron trafficking drives ferroptotic cell death. Nature communications 1 41407700
2024 Exosomes derived from umbilical cord mesenchymal stem cells ameliorate ischemic brain injury in mice by regulating AAK1 via miR-664a-5p. The International journal of neuroscience 1 39655875
2023 AAK1-like: A putative pseudokinase with potential roles in cargo uptake in bloodstream form Trypanosoma brucei parasites. The Journal of eukaryotic microbiology 1 37548427
2026 Genetic variations in AAK1 and ADAM17 associated with circulatory cytokines changes influence COVID-19 susceptibility and severity. Human genomics 0 41761307
2026 AAK1-mediated phosphorylation of PDLIM5 and Talin1 promotes focal adhesion disassembly to accelerate cell migration. Nature communications 0 42082516
2024 Discovery and evaluation of HW161023 as a potent and orally active AAK1 inhibitor. Bioorganic & medicinal chemistry letters 0 39486488

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