Affinage

GAK

Cyclin-G-associated kinase · UniProt O14976

Length
1311 aa
Mass
143.2 kDa
Annotated
2026-04-28
51 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GAK (cyclin G-associated kinase/auxilin 2) is a constitutively active serine/threonine kinase that orchestrates clathrin-coated vesicle dynamics, mitotic spindle integrity, autophagy, and actomyosin regulation. Its J-domain recruits and activates Hsc70 to drive clathrin lattice remodeling and uncoating at coated pits—essential for stabilizing and invaginating nascent clathrin-coated pits during endocytosis—while its PTEN-like domain mediates phospholipid-dependent membrane recruitment, and its kinase domain phosphorylates the AP2 medium subunit (AP2M1) and the Na⁺/K⁺-ATPase subunit Atp1a3 to regulate cargo trafficking (PMID:12010461, PMID:16895969, PMID:40424130, PMID:30623173). Beyond endocytosis, GAK cooperates with clathrin heavy chain to maintain centrosome maturation and chromosome congression during mitosis, promotes Parkin-independent mitophagy through kinase-dependent modulation of mitochondrial and lysosomal networks, controls glial autophagy initiation via ULK1/Atg1 interaction through its uncoating domain, and antagonizes ROCK-dependent actomyosin contractility through its intrinsically disordered region via binding the RhoGEF ARHGEF2 (PMID:19654208, PMID:34671015, PMID:37428930, PMID:41995027). GAK undergoes cell-cycle-dependent nuclear–cytoplasmic redistribution regulated by c-Src phosphorylation at Y412/Y1149, and its protein levels are controlled by FBXO22-mediated ubiquitin-dependent proteasomal degradation (PMID:28135906, PMID:37442264).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1997 High

    Establishing that GAK is a kinase associated with cell-cycle regulators resolved the question of what enzyme partners with cyclin G, revealing GAK as a kinase with a C-terminal auxilin-like domain whose expression peaks at G1.

    Evidence Co-immunoprecipitation, BIAcore binding, and synchronized HeLa cell kinase assays

    PMID:9013862 PMID:9299234

    Open questions at the time
    • Physiological substrates of the kinase domain unknown
    • Functional significance of cyclin G interaction not determined
    • No loss-of-function data
  2. 2002 High

    Identification of GAK as the major CCV-associated kinase that directly phosphorylates the AP2 mu2 subunit connected its kinase activity to clathrin-coated vesicle biology, answering what kinase modifies AP2 in vivo.

    Evidence In vitro kinase assay with purified CCVs and recombinant substrates

    PMID:12010461

    Open questions at the time
    • Functional consequence of mu2 phosphorylation by GAK on cargo sorting not demonstrated
    • Redundancy with other CCV kinases unclear
  3. 2005 High

    GAK depletion established that GAK is required not only for clathrin uncoating but also for maintaining adaptor and clathrin association with membranes, broadening its role from uncoating factor to general clathrin-coat organizer.

    Evidence shRNA knockdown in HeLa cells with transferrin/EGF internalization assays and adaptor localization

    PMID:16155256

    Open questions at the time
    • Mechanism by which GAK/Hsc70 promotes adaptor-membrane binding not resolved
    • Contribution of kinase activity vs. J-domain not separated
  4. 2006 High

    Live imaging revealed the spatiotemporal order of GAK action at coated pits—recruited after dynamin via its PTEN-like domain—resolving when and how GAK engages the endocytic machinery.

    Evidence TIRF microscopy in live cells with domain-mapping experiments

    PMID:16895969

    Open questions at the time
    • Signal that triggers GAK release from the membrane post-uncoating unclear
    • Lipid species specificity of the PTEN-like domain not defined
  5. 2009 High

    Discovery that GAK cooperates with clathrin heavy chain to regulate centrosome maturation and chromosome congression revealed a non-endocytic, mitotic function for GAK, answering why GAK depletion causes metaphase arrest.

    Evidence siRNA knockdown with immunofluorescence of mitotic spindles and co-IP of GAK–CHC

    PMID:19654208

    Open questions at the time
    • Whether kinase activity or J-domain is required for mitotic function not separated
    • Substrates at the centrosome not identified
  6. 2011 High

    The kinase-dead knock-in mouse established that GAK kinase activity is essential for neonatal survival and pulmonary surfactant secretion, answering whether catalytic activity is required in vivo beyond its scaffolding/chaperone functions.

    Evidence GAK kinase-dead knock-in mouse with histological and molecular analysis of lungs

    PMID:22022498

    Open questions at the time
    • Direct kinase substrates required for surfactant secretion not identified
    • Whether surfactant defect is trafficking- or transcription-based not resolved
  7. 2014 High

    Crystallographic resolution of GAK's constitutively active kinase domain and its unusual dimeric autoinhibited state provided the first structural framework for understanding GAK regulation and inhibitor design.

    Evidence X-ray crystallography of apo and nanobody-bound GAK kinase domain with enzyme kinetics

    PMID:24438162

    Open questions at the time
    • How dimerization-based autoinhibition is relieved in cells unknown
    • Full-length structural context absent
  8. 2015 High

    Domain-rescue experiments in GAK-knockout mice demonstrated that the clathrin-binding and J-domains are the minimal unit sufficient for clathrin chaperoning and in vivo viability, clarifying which domains execute the core uncoating function.

    Evidence Transgenic rescue of tissue-specific GAK knockout mice and knockout fibroblasts with domain fragments

    PMID:26345367

    Open questions at the time
    • PTEN-like domain contribution in neurons and other tissues not fully excluded
    • Kinase domain contribution assessed only indirectly
  9. 2017 Medium

    Identification of c-Src-mediated phosphorylation at Y412/Y1149 and cell-cycle-dependent nuclear–cytoplasmic redistribution of phospho-GAK connected GAK to upstream tyrosine kinase signaling and suggested a role at chromosomes during mitosis.

    Evidence Phospho-specific antibodies, immunofluorescence through mitosis, mass spectrometry identifying MCM3 association

    PMID:28135906

    Open questions at the time
    • Functional consequence of Y412/Y1149 phosphorylation on GAK activity not tested
    • MCM3 interaction not validated reciprocally
    • c-Src–GAK axis not confirmed in vivo
  10. 2018 High

    Chemical-genetic identification of Atp1a3 as a GAK substrate in neurons, combined with electrophysiology in conditional knockout mice, established that GAK phosphorylation regulates Na⁺/K⁺-ATPase surface trafficking in the brain.

    Evidence Analog-sensitive GAK kinase allele, whole-cell patch clamp in conditional knockout CA1 neurons

    PMID:30623173

    Open questions at the time
    • Phosphosite(s) on Atp1a3 not mapped
    • Whether this applies to non-neuronal tissues unknown
  11. 2021 High

    A systematic screen revealed GAK as a kinase-dependent positive regulator of Parkin-independent mitophagy, conserved to C. elegans, establishing a new role for GAK in selective organelle quality control distinct from bulk autophagy.

    Evidence siRNA screen of 197 lipid-binding proteins, kinase-activity requirement, C. elegans gakh-1 knockdown

    PMID:34671015

    Open questions at the time
    • Direct mitophagy substrates of GAK kinase unknown
    • Mechanism linking GAK to mitophagy receptor engagement not defined
  12. 2021 Medium

    GAK knockout impairs autophagosome–lysosome fusion and autophagic lysosome reformation through ROCK-actomyosin dysregulation, revealing GAK as an upstream negative regulator of ROCK signaling in lysosomal dynamics.

    Evidence CRISPR knockout, chemical GAK inhibition, ROCK inhibitor and ROCK1 siRNA rescue in A549 cells

    PMID:34468012

    Open questions at the time
    • Whether GAK acts on ROCK directly or via an intermediate not resolved
    • Contribution of kinase vs. scaffolding function not dissected
  13. 2023 High

    Identification of GAK's interaction with ULK1/Atg1 via its uncoating domain in Drosophila glia and mouse microglia established that GAK controls autophagy initiation by regulating Atg1/Atg9 trafficking to autophagosomes, distinct from its endocytic role.

    Evidence Co-IP of GAK with ULK1/Atg1, Drosophila dAux knockout, mouse microglia GAK loss-of-function, autophagosome imaging

    PMID:37428930

    Open questions at the time
    • Whether ULK1 interaction is direct or mediated by clathrin not fully resolved
    • Relevance to non-glial cell types not tested
  14. 2023 Medium

    FBXO22 was identified as the E3 ubiquitin ligase targeting GAK for proteasomal degradation, revealing how GAK protein levels are regulated post-translationally.

    Evidence Proteomics, FBXO22 overexpression/depletion, proteasome inhibitor rescue, ubiquitination assay in cervical cancer cells

    PMID:37442264

    Open questions at the time
    • Degron motif on GAK not mapped
    • Physiological context triggering FBXO22-dependent GAK turnover unknown
    • Single cell-type study
  15. 2025 High

    J-domain mutagenesis with quantitative live CCP tracking demonstrated that GAK-Hsc70 remodels nascent clathrin lattices to promote CCP stabilization and curvature development, resolving the long-standing question of whether GAK acts only after vesicle scission or also during pit maturation.

    Evidence GAK knockdown and J-domain point mutants with TIRF microscopy tracking of individual CCP lifetimes

    PMID:40424130

    Open questions at the time
    • Whether Hsc70-dependent remodeling requires GAK kinase activity not tested
    • Structural intermediates of lattice remodeling not visualized
  16. 2026 High

    Identification of GAK's intrinsically disordered region as the functional domain that antagonizes ROCK-dependent actomyosin contractility via direct ARHGEF2 binding separated this kinase-independent scaffolding role from GAK's catalytic functions.

    Evidence CRISPR KO, IDR vs. kinase domain rescue, co-IP of GAK IDR with ARHGEF2, ARHGEF2 siRNA epistasis

    PMID:41995027

    Open questions at the time
    • How GAK IDR inhibits ARHGEF2 GEF activity mechanistically unknown
    • Whether IDR-ARHGEF2 axis operates in non-epithelial contexts not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include the identity of direct mitophagy-relevant substrates of GAK kinase, the structural basis of full-length GAK autoinhibition and activation, and the integration of its kinase-dependent and kinase-independent functions in tissue-specific contexts such as neurodegeneration.
  • No full-length structure or cryo-EM model exists
  • Direct phosphorylation targets in mitophagy pathway unidentified
  • Disease-relevant (e.g. Parkinson's GWAS locus) mechanism of GAK not experimentally resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0044183 protein folding chaperone 2 GO:0098772 molecular function regulator activity 2 GO:0060090 molecular adaptor activity 1
Localization
GO:0031410 cytoplasmic vesicle 4 GO:0005634 nucleus 2 GO:0005815 microtubule organizing center 2 GO:0005886 plasma membrane 2 GO:0005829 cytosol 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 5 R-HSA-9612973 Autophagy 4 R-HSA-1640170 Cell Cycle 3 R-HSA-382551 Transport of small molecules 2
Partners
AP2M1ARHGEF2ATP1A3CCNG1CLTCFBXO22HSPA8ULK1
Complex memberships
Clathrin-coated vesicle coatGAK-Hsc70 uncoating complex

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 GAK (cyclin G-associated kinase) was identified as a direct binding partner of cyclin G and CDK5. GAK contains an N-terminal Ser/Thr kinase domain and a C-terminal tensin/auxilin-like domain with a leucine zipper region. Co-immunoprecipitation and BIAcore analysis confirmed direct GAK–cyclin G interaction in vivo. West-Western blotting, co-immunoprecipitation, BIAcore (surface plasmon resonance) FEBS letters High 9013862
1997 GAK expression peaks at G1 phase during the cell cycle, and immunoprecipitates of anti-cyclin G antibody show histone H1 kinase activity that fluctuates during the cell cycle with a peak at G1 phase, suggesting GAK is an active kinase in the cyclin G complex. Synchronized HeLa cell cycle analysis, kinase assay of anti-cyclin G immunoprecipitates, Northern blot Genomics Medium 9299234
2002 GAK/auxilin2 is a major protein kinase in clathrin-coated vesicles (CCVs) and directly phosphorylates the AP2 medium subunit (mu2/AP2M1), both in intact CCVs and in solution, distinguishing it from CK2 which phosphorylates other CCV-associated proteins. Isolation of purified CCVs from porcine brain, in vitro kinase assay with CCV peripheral membrane proteins as substrate, antibody identification Traffic (Copenhagen, Denmark) High 12010461
2005 Depletion of GAK by shRNA in HeLa cells inhibited receptor-mediated endocytosis (transferrin and EGF internalization), reduced clathrin-coated pits on the plasma membrane, and dramatically decreased AP2 and epsin on the plasma membrane and AP1/GGA at the trans-Golgi network, indicating GAK (together with Hsc70) mediates binding of clathrin and adaptors to membranes in addition to clathrin uncoating. Vector-based shRNA knockdown, fluorescence microscopy, transferrin/EGF internalization assays, dominant-negative Hsp70 expression Journal of cell science High 16155256
2006 GAK is transiently recruited to clathrin-coated pits (CCPs) after dynamin, immediately before vesicle invagination. GAK recruitment depends on its PTEN-like domain, which binds phospholipids. GAK recruitment is required for Hsc70-dependent irreversible clathrin uncoating, and both vesicle budding and synchronous GAK recruitment are necessary for uncoating. Total internal reflectance fluorescence (TIRF) microscopy in live cells, actin depolymerization experiments, domain mapping Journal of cell science High 16895969
2009 GAK is required for proper centrosome maturation and mitotic chromosome congression. GAK knockdown by siRNA caused metaphase arrest via spindle-assembly checkpoint activation, multi-aster formation due to abnormal pericentriolar material fragmentation, and GAK cooperates with clathrin heavy chain (CHC) in the same pathway during mitosis, interacting with CHC to regulate functional spindle formation. siRNA knockdown, immunofluorescence microscopy, cell cycle analysis, co-immunoprecipitation Journal of cell science High 19654208
2009 GAK localizes in both cytoplasm and nucleus. In the nucleus, GAK forms complexes with cyclin G1, p53, clathrin heavy chain (CHC), and protein phosphatase 2A B'alpha1. CHC associates with GAK via a different domain depending on cytoplasmic vs. nuclear context. Approximately 20–30% of B'alpha1, cyclin G1, and p53 complex with nuclear GAK. Immunostaining, GFP-GAK ectopic expression, pull-down assays with dissected GAK fragments, co-immunoprecipitation Genes to cells Medium 19371378
2010 In zebrafish, knockdown of GAK (ubiquitously expressed auxilin ortholog) increases neuronal cell specification and decreases expression of the Notch target gene Her4, placing GAK upstream of Notch-dependent neuronal patterning. GAK knockdown also caused elevated apoptosis in neural tissues. Morpholino-mediated knockdown in zebrafish, gene expression analysis, functional complementation with Drosophila auxilin BMC developmental biology Medium 20082716
2011 Mice expressing a kinase-dead form of GAK (GAK-kd knockout) die within 30 min after birth due to respiratory/pulmonary dysfunction. Surfactant protein A was abundant within alveolar spaces of control but absent in GAK-kd mice, and E-cadherin and phosphorylated EGFR signals were abnormal, establishing that GAK kinase activity is essential for pulmonary alveolar function. Kinase-dead knock-in mouse model, immunohistochemistry, histological analysis PloS one High 22022498
2014 Crystal structure of the GAK catalytic domain revealed it is constitutively active and can adopt a dimeric inactive state via an unusual activation segment interaction in the apo form. Nanobody co-crystallization captured distinct conformations: one nanobody (NbGAK_4) stabilized the dimeric inactive state, while another (NbGAK_1) captured a monomeric active conformation with a well-ordered activation segment. GAK is an ATP-competitive kinase. X-ray crystallography of GAK catalytic domain alone and in complex with nanobodies, enzyme kinetic assays The Biochemical journal High 24438162
2015 The clathrin-binding domain and J-domain of GAK are sufficient for Hsc70-dependent clathrin chaperoning and uncoating. A 62-kDa fragment comprising only the clathrin-binding and J-domains rescued clathrin-dependent trafficking in GAK-knockout fibroblasts and rescued lethality from brain- or liver-specific GAK knockout in mice. The PTEN-like domain is not essential for these core chaperone functions but increases efficiency in certain tissues. Domain-deletion rescue experiments in knockout fibroblasts, transgenic mouse rescue of tissue-specific GAK KO, double KO (GAK + auxilin) in brain Journal of cell science High 26345367
2015 Selective GAK inhibitors (isothiazolo[5,4-b]pyridines) act as type I ATP-competitive inhibitors of GAK and inhibit hepatitis C virus (HCV) at two distinct steps: viral entry and assembly, establishing that GAK kinase activity regulates HCV intracellular trafficking. Co-crystallization with GAK, antiviral assays, kinase inhibition assays Journal of medicinal chemistry High 25822739
2017 The lncRNA OIP5-AS1 directly binds GAK mRNA in the cytoplasm, reducing GAK mRNA stability and protein abundance. Elevated GAK levels after OIP5-AS1 silencing cause aberrant mitotic spindles; simultaneous silencing of both OIP5-AS1 and GAK partially rescues the mitotic defect, placing GAK downstream of OIP5-AS1 in regulation of mitotic progression. RNA pulldown, mRNA stability assays, siRNA double knockdown rescue experiments, immunofluorescence of mitotic spindles Oncotarget Medium 28472763
2017 GAK is phosphorylated by c-Src at Y412 and Y1149. Phosphorylated GAK (pY412/pY1149) translocates from nucleus during interphase to chromosomes at prophase/prometaphase, to centrosomes at metaphase, then back to chromosomes at telophase. Mass spectrometry and co-immunoprecipitation identified MCM3 (DNA licensing factor) as a GAK-associated protein, suggesting a c-Src–GAK–MCM3 axis in DNA replication licensing. Phospho-specific antibody, immunofluorescence, mass spectrometry, co-immunoprecipitation/Western blot Cell cycle Medium 28135906
2018 Using a chemical genetics approach (analog-sensitive GAK), GAK was shown to phosphorylate the Na+/K+-ATPase alpha-subunit Atp1a3. GAK conditional knockout neurons (CA1 pyramidal) showed a larger resting membrane potential change upon Na+/K+-ATPase blockade (ouabain), establishing that GAK regulates Na+/K+-ATPase trafficking to the plasma membrane via phosphorylation of Atp1a3. Chemical genetics (analog-sensitive kinase), whole-cell patch clamp recordings, conditional knockout mice Life science alliance High 30623173
2019 Live imaging siRNA screen identified GAK as required for proper spindle positioning in human cells. GAK depletion impairs astral microtubules, similar to downregulation of its interactor Clathrin, placing GAK-Clathrin interaction upstream of astral microtubule integrity during mitosis. Live imaging siRNA screen on fibronectin micropatterns, immunofluorescence, clathrin depletion comparison Nature communications Medium 31253758
2021 GAK and PRKCD are positive regulators of PRKN-independent mitophagy, dispensable for PRKN-dependent mitophagy and starvation-induced autophagy. GAK kinase activity is required for efficient mitophagy in vitro. In vivo, knockdown of the C. elegans GAK homolog (gakh-1) significantly inhibits basal mitophagy, demonstrating evolutionary conservation. siRNA library screen targeting 197 lipid-binding proteins, kinase activity requirement assays, C. elegans gakh-1 knockdown, zebrafish PRKCD knockout Nature communications High 34671015
2021 GAK controls lysosomal dynamics via actomyosin regulation during autophagy. GAK knockout in A549 cells impaired autophagosome–lysosome fusion and autophagic lysosome reformation, causing accumulation of enlarged autophagosomes and autolysosomes. ROCK inhibition or ROCK1 knockdown mitigated GAK-KO-mediated defects, placing GAK upstream of ROCK-actomyosin signaling in lysosomal dynamics. GAK CRISPR/Cas9 knockout, GAK chemical inhibition, autophagic flux analysis, live imaging of lysosomes, ROCK inhibitor rescue, ROCK1 siRNA rescue International journal of molecular medicine Medium 34468012
2022 GAK activity modifies the mitochondrial network and lysosomal morphology that are required for efficient mitochondrial transport to lysosomes during PRKN-independent mitophagy, while PRKCD localizes to mitochondria and regulates ULK1-ATG13 recruitment to early autophagic structures. GAK/PRKCD kinase inhibition, fluorescence microscopy of mitochondrial network and lysosomes, ULK1-ATG13 recruitment assay Autophagy Medium 35001811
2023 GAK/dAux (Drosophila homolog) interacts with the autophagy initiation kinase ULK1/Atg1 via its uncoating domain and regulates trafficking of Atg1 and Atg9 to autophagosomes in glia, controlling the onset of glial autophagy. Lack of GAK/dAux increases autophagosome number and size and upregulates components of the initiation and PI3K class III complexes. Drosophila dAux knockout/knockdown, co-immunoprecipitation of GAK with ULK1/Atg1, mouse microglia GAK loss-of-function, autophagosome imaging Proceedings of the National Academy of Sciences of the United States of America High 37428930
2023 FBXO22 mediates ubiquitin-dependent proteasomal degradation of GAK in cervical cancer cells, as established by proteomics, comparison of protein decay rates in cells with altered FBXO22 abundance, proteasome inhibitor rescue, and cellular ubiquitination assays. Proteomics, FBXO22 overexpression/depletion, proteasome inhibitor treatment, protein decay rate comparison, cellular ubiquitination assay Experimental cell research Medium 37442264
2025 GAK knockdown inhibits clathrin-coated pit (CCP) stabilization and invagination. Mutations in the J-domain of GAK that abolish Hsc70 recruitment to and activation at CCPs cause accumulation of GAK at CCPs, hinder CCP stabilization and invagination, and dramatically increase abortive (highly transient) CCPs. This establishes that GAK-Hsc70 promotes turnover and remodeling of nascent clathrin assemblies required for curvature development during clathrin-mediated endocytosis. GAK knockdown, J-domain mutagenesis, live TIRF microscopy tracking of CCP dynamics, quantification of abortive CCPs Proceedings of the National Academy of Sciences of the United States of America High 40424130
2026 GAK antagonizes ROCK-dependent actomyosin dynamics via its intrinsically disordered region (IDR), not its kinase domain. GAK-KO cells show enhanced stress fiber formation, increased myosin light chain (MLC) phosphorylation, and increased cell migration. The GAK IDR directly interacts with ARHGEF2 (a RhoGEF), and ARHGEF2 knockdown suppresses stress fiber formation in GAK-KO cells. The GAK IDR also contributes to regulation of MLC expression. CRISPR/Cas9 GAK knockout, domain rescue (IDR vs kinase), co-immunoprecipitation of GAK IDR with ARHGEF2, ARHGEF2 siRNA epistasis, MLC phosphorylation assays, cell migration assays Journal of cell science High 41995027

Source papers

Stage 0 corpus · 51 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 GAK: a cyclin G associated kinase contains a tensin/auxilin-like domain. FEBS letters 113 9013862
2006 Recruitment dynamics of GAK and auxilin to clathrin-coated pits during endocytosis. Journal of cell science 102 16895969
2002 CK2 and GAK/auxilin2 are major protein kinases in clathrin-coated vesicles. Traffic (Copenhagen, Denmark) 84 12010461
2005 Depletion of GAK/auxilin 2 inhibits receptor-mediated endocytosis and recruitment of both clathrin and clathrin adaptors. Journal of cell science 72 16155256
2009 GAK, a regulator of clathrin-mediated membrane traffic, also controls centrosome integrity and chromosome congression. Journal of cell science 65 19654208
2021 GAK and PRKCD are positive regulators of PRKN-independent mitophagy. Nature communications 57 34671015
1997 Structure, expression, and chromosomal localization of human GAK. Genomics 52 9299234
2010 Replication of GWAS associations for GAK and MAPT in Parkinson's disease. Annals of human genetics 50 21058943
2015 Selective Inhibitors of Cyclin G Associated Kinase (GAK) as Anti-Hepatitis C Agents. Journal of medicinal chemistry 47 25822739
2014 Structure of cyclin G-associated kinase (GAK) trapped in different conformations using nanobodies. The Biochemical journal 47 24438162
2019 SGC-GAK-1: A Chemical Probe for Cyclin G Associated Kinase (GAK). Journal of medicinal chemistry 42 30768268
2018 Optimization of Isothiazolo[4,3- b]pyridine-Based Inhibitors of Cyclin G Associated Kinase (GAK) with Broad-Spectrum Antiviral Activity. Journal of medicinal chemistry 32 29953812
2017 LncRNA OIP5-AS1/cyrano suppresses GAK expression to control mitosis. Oncotarget 32 28472763
2019 Design of a Cyclin G Associated Kinase (GAK)/Epidermal Growth Factor Receptor (EGFR) Inhibitor Set to Interrogate the Relationship of EGFR and GAK in Chordoma. Journal of medicinal chemistry 27 30973735
2009 GAK, a regulator of clathrin-mediated membrane trafficking, localizes not only in the cytoplasm but also in the nucleus. Genes to cells : devoted to molecular & cellular mechanisms 27 19371378
2011 Neonatal lethality in knockout mice expressing the kinase-dead form of the gefitinib target GAK is caused by pulmonary dysfunction. PloS one 23 22022498
2015 The clathrin-binding and J-domains of GAK support the uncoating and chaperoning of clathrin by Hsc70 in the brain. Journal of cell science 22 26345367
2019 Utilizing comprehensive and mini-kinome panels to optimize the selectivity of quinoline inhibitors for cyclin G associated kinase (GAK). Bioorganic & medicinal chemistry letters 19 31129055
2016 The 4p16.3 Parkinson Disease Risk Locus Is Associated with GAK Expression and Genes Involved with the Synaptic Vesicle Membrane. PloS one 19 27508417
2013 Genetic variations of GAK in two Chinese Parkinson's disease populations: a case-control study. PloS one 19 23826309
2022 GAK and PRKCD kinases regulate basal mitophagy. Autophagy 16 35001811
2019 Design and Analysis of the 4-Anilinoquin(az)oline Kinase Inhibition Profiles of GAK/SLK/STK10 Using Quantitative Structure-Activity Relationships. ChemMedChem 16 31675459
2018 Cyclin G-associated kinase (GAK) affinity and antiviral activity studies of a series of 3-C-substituted isothiazolo[4,3-b]pyridines. European journal of medicinal chemistry 16 30529544
2011 GWAS-linked GAK locus in Parkinson's disease in Han Chinese and meta-analysis. Human genetics 16 22198721
2016 miR-206 inhibits renal cell cancer growth by targeting GAK. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban 15 27924503
2013 Reaffirmation of GAK, but not HLA-DRA, as a Parkinson's disease susceptibility gene in a Taiwanese population. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 15 24039160
2010 Disruption of zebrafish cyclin G-associated kinase (GAK) function impairs the expression of Notch-dependent genes during neurogenesis and causes defects in neuronal development. BMC developmental biology 14 20082716
2021 Targeted disruption of GAK stagnates autophagic flux by disturbing lysosomal dynamics. International journal of molecular medicine 13 34468012
2019 Towards the Development of an In vivo Chemical Probe for Cyclin G Associated Kinase (GAK). Molecules (Basel, Switzerland) 13 31698822
2023 Cyclin-G-associated kinase GAK/dAux regulates autophagy initiation via ULK1/Atg1 in glia. Proceedings of the National Academy of Sciences of the United States of America 12 37428930
2020 Targeting the Water Network in Cyclin G-Associated Kinase (GAK) with 4-Anilino-quin(az)oline Inhibitors. ChemMedChem 11 32358915
2015 Interaction between SNCA, LRRK2 and GAK increases susceptibility to Parkinson's disease in a Chinese population. eNeurologicalSci 11 29479569
2015 Genome-wide haplotype association analysis identifies SERPINB9, SERPINE2, GAK, and HSP90B1 as novel risk genes for oral squamous cell carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 10 26318431
2015 Quantitative assessment of the association between GAK rs1564282 C/T polymorphism and the risk of Parkinson's disease. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 9 25975492
2024 Back-Pocket Optimization of 2-Aminopyrimidine-Based Macrocycles Leads to Potent EPHA2/GAK Kinase Inhibitors. Journal of medicinal chemistry 8 39028937
2019 SNCA but not DNM3 and GAK modifies age at onset of LRRK2-related Parkinson's disease in Chinese population. Journal of neurology 8 31041581
2018 Chemical genetic identification of GAK substrates reveals its role in regulating Na+/K+-ATPase. Life science alliance 8 30623173
2013 A kinome-wide siRNA screen identifies multiple roles for protein kinases in hypoxic stress adaptation, including roles for IRAK4 and GAK in protection against apoptosis in VHL-/- renal carcinoma cells, despite activation of the NF-κB pathway. Journal of biomolecular screening 7 23591012
2015 The Potential Mutation of GAK Gene in the Typical Sporadic Parkinson's Disease from the Han Population of Chinese Mainland. Molecular neurobiology 6 26676575
2023 FBXO22 inhibits proliferation and metastasis of cervical cancer cells by mediating ubiquitination-dependent degradation of GAK. Experimental cell research 5 37442264
2019 Live imaging screen reveals that TYRO3 and GAK ensure accurate spindle positioning in human cells. Nature communications 5 31253758
2017 GAK is phosphorylated by c-Src and translocated from the centrosome to chromatin at the end of telophase. Cell cycle (Georgetown, Tex.) 4 28135906
1984 [A newly established melanoma cell line (GAK) with 5-S-cysteinyldopa phenotype]. Nihon Sanka Fujinka Gakkai zasshi 4 6431036
2022 The cyclin G-associated kinase (GAK) inhibitor SGC-GAK-1 inhibits neurite outgrowth and synapse formation. Molecular brain 3 35883152
2025 Dynamic early recruitment of GAK-Hsc70 regulates coated pit maturation. Proceedings of the National Academy of Sciences of the United States of America 2 40424130
2024 Synthesis and evaluation of isothiazolo[4,5-b]pyridines as cyclin G-associated kinase (GAK) inhibitors. Organic & biomolecular chemistry 1 39171941
2026 Genome-wide association study identifies GAK and KLF12 associated with curve severity of adolescent idiopathic scoliosis. PeerJ 0 41584833
2026 GAK antagonises ROCK-dependent regulation of actomyosin dynamics. Journal of cell science 0 41995027
2025 Low-frequency genetic variants in GAK enhance Golgi function and protect against Parkinson's disease. medRxiv : the preprint server for health sciences 0 40832425
2024 Back-pocket optimization of 2-aminopyrimidine-based macrocycles leads to potent dual EPHA2/GAK kinase inhibitors with antiviral activity. bioRxiv : the preprint server for biology 0 38405908
2024 The cyclin-G associated kinase (GAK) is a novel mitotic kinase and therapeutic target in diffuse large B-cell lymphoma. bioRxiv : the preprint server for biology 0 39484514