Affinage

AXL

Tyrosine-protein kinase receptor UFO · UniProt P30530

Length
894 aa
Mass
98.3 kDa
Annotated
2026-04-28
100 papers in source corpus 32 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AXL is a TAM-family receptor tyrosine kinase that functions as a key regulator of cell survival, migration, efferocytosis, and immune modulation through Gas6- and Protein S-dependent activation of PI3K/AKT, MAPK, Src/FAK/NFκB, and Rac1 signaling cascades (PMID:16362042, PMID:25332238, PMID:16627783, PMID:23318455). Gas6 binding to the two immunoglobulin-like domains of AXL drives formation of a 2:2 ligand–receptor complex that triggers autophosphorylation, and AXL further diversifies signaling by heterodimerizing with EGFR and HER3 to sustain survival during targeted therapy (PMID:16362042, PMID:30651547). AXL protein levels are tightly controlled through c-Cbl-mediated ubiquitination and lysosomal degradation, LZTR1-CUL3 ubiquitin ligase-directed turnover, p85β/TRIM2/optineurin-dependent autophagic clearance, GALNT2-mediated O-glycosylation, ectodomain shedding, and post-transcriptional regulation of its mRNA by PTBP1 and NAT10 (PMID:15958209, PMID:36445254, PMID:32385243, PMID:36409270, PMID:7822279, PMID:31729427, PMID:37156457). Beyond canonical RTK signaling, AXL mediates efferocytosis through an LRP-1/RANBP9 complex in dendritic cells, facilitates endothelial uptake of platelet-derived microparticles, and suppresses TP53 transcription via direct promoter binding (PMID:24509082, PMID:27006397, PMID:32992696).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1993 Medium

    Characterization of the AXL genomic locus revealed a GC-rich, TATA-less promoter with Sp1/AP-2/CREB sites and alternative splicing of exon 10, establishing the basic transcriptional architecture of the gene.

    Evidence Genomic library screening, S1 nuclease/primer extension mapping of the human AXL locus

    PMID:8381225

    Open questions at the time
    • Functional significance of individual promoter elements not tested by mutagenesis
    • Role of alternative splicing isoforms undefined
  2. 1995 High

    Discovery that AXL undergoes proteolytic ectodomain shedding near its transmembrane domain established a first mechanism for downregulating surface AXL and generating soluble receptor.

    Evidence Biochemical characterization of AXL cleavage products with phorbol ester stimulation and turnover assays

    PMID:7822279

    Open questions at the time
    • Identity of the responsible protease not determined
    • Physiological stimuli beyond phorbol esters not explored
  3. 1999 Medium

    Identification of E1A as a transcriptional repressor of AXL, with Gas6/AXL signaling opposing E1A-mediated growth suppression, linked AXL to survival signaling for the first time.

    Evidence Degenerate RT-PCR kinase profiling, AXL cDNA rescue, Gas6 stimulation, and serum deprivation apoptosis assay

    PMID:10567533

    Open questions at the time
    • Mechanism of E1A-mediated transcriptional repression of AXL not defined
    • Downstream survival pathway not specified beyond anti-apoptosis
  4. 2003 Medium

    Demonstration that autocrine Gas6 activates AXL in vascular pericytes and that decoy receptor blockade promotes osteogenic differentiation established AXL as a tonic suppressor of cell fate transitions.

    Evidence Soluble AXL ectodomain treatment with phospho-AXL and mineralization readouts in pericyte cultures

    PMID:12730092

    Open questions at the time
    • Downstream pathway connecting AXL to osteogenic transcription not identified
    • Single cell type studied
  5. 2005 High

    The 3.3 Å crystal structure of Gas6/AXL resolved how two AXL Ig-like domains are crosslinked by Gas6 LG1 in a 2:2 complex with no direct receptor–receptor contacts, defining the unique activation mechanism of AXL.

    Evidence X-ray crystallography with structure-based mutagenesis and receptor activation assays

    PMID:16362042

    Open questions at the time
    • Conformational changes in the intracellular kinase domain upon dimerization not resolved
    • Full-length receptor structure unavailable
  6. 2005 Medium

    Gas6-induced AXL ubiquitination was shown to be c-Cbl-dependent and to drive lysosomal (not proteasomal) degradation, distinguishing AXL turnover from many other RTKs.

    Evidence Pharmacological inhibition of endocytosis/lysosomes/proteasome, immunoprecipitation, and ubiquitination assays

    PMID:15958209

    Open questions at the time
    • Direct E3 ligase assay for c-Cbl on AXL not performed
    • Ubiquitin chain type not determined
  7. 2006 High

    Axl−/− mice showed impaired flow-dependent vascular remodeling with increased apoptosis and reduced p-Akt, genetically placing AXL upstream of Akt-dependent survival in vascular smooth muscle cells in vivo.

    Evidence Axl knockout mice with carotid ligation, immunohistochemistry, and Western blot for p-Akt

    PMID:16627783

    Open questions at the time
    • Whether AXL signals to Akt directly or through PI3K intermediates not resolved in this model
    • Contribution of other TAM receptors not excluded
  8. 2010 High

    AXL was identified as an enhancer of macropinocytosis-dependent Ebola virus entry, revealing a role for AXL in regulating a specific endocytic pathway exploited by enveloped viruses.

    Evidence RNAi knockdown, dominant-negative constructs, and pathway-specific inhibitors with infection assays

    PMID:21047970

    Open questions at the time
    • Whether AXL acts as a direct virus receptor or enhances macropinocytosis indirectly not fully resolved
    • Mechanism by which AXL activates macropinocytosis not defined
  9. 2013 Medium

    Mapping of a Src/FAK/NFκB cascade downstream of Gas6/AXL in schwannoma cells, with merlin as a negative regulator and CRL4-DCAF1 as a positive regulator, provided the first defined multi-node signaling pathway linking AXL to NFκB-dependent gene targets (survivin, cyclin D1).

    Evidence Gas6 stimulation, shRNA knockdown, and signaling/functional assays in schwannoma cells

    PMID:23318455

    Open questions at the time
    • Direct phosphorylation targets linking AXL to Src not identified
    • Whether merlin-AXL regulation is direct or indirect not established
  10. 2014 High

    Identification of Elmo1/2 as direct AXL substrates phosphorylated on Tyr-713 established the first biochemically validated AXL kinase substrate and connected AXL to Rac1 activation via Dock GEFs.

    Evidence Proteomics, mutagenesis (Y713F), co-IP, Rac1 activation, and invasion assays in breast cancer cells

    PMID:25332238

    Open questions at the time
    • Whether Elmo phosphorylation is required for non-cancer AXL functions (e.g., efferocytosis) not tested
    • Structural basis of AXL-Elmo recognition unknown
  11. 2014 High

    Discovery that AXL forms a tripartite complex with LRP-1 and RANBP9 in dendritic cells, where AXL recognizes apoptotic cells but LRP-1 is required for internalization, defined a cooperative receptor mechanism for efferocytosis and antigen cross-presentation.

    Evidence Targeted gene deletion in mice, co-IP, in vivo efferocytosis, and antigen cross-presentation assays

    PMID:24509082

    Open questions at the time
    • Signaling events downstream of AXL-LRP-1-RANBP9 complex not characterized
    • Whether this complex operates in non-dendritic phagocytes unknown
  12. 2016 Medium

    AXL heterodimerization with EGFR was shown to bypass anti-EGFR and PI3K inhibitor therapy through activation of a PLCγ–PKC–mTORC1 bypass pathway, providing a mechanistic basis for AXL-driven drug resistance.

    Evidence Receptor co-immunoprecipitation, signaling analysis, and pharmacological inhibition in cancer cell lines

    PMID:26763248

    Open questions at the time
    • Whether AXL-EGFR heterodimer forms through direct extracellular or intracellular interaction not defined
    • Structural basis of heterodimerization unknown
  13. 2016 Medium

    AP-1 transcription factors c-JUN and c-FOS were identified as direct transcriptional activators of AXL, and their silencing restored drug sensitivity, establishing the upstream transcriptional control of AXL expression in resistant tumors.

    Evidence siRNA silencing, qPCR/Western blot, JNK inhibitor studies, and xenograft models

    PMID:30860495

    Open questions at the time
    • Direct AP-1 binding to AXL promoter not demonstrated by ChIP in this study
    • Relative contribution of c-JUN vs. c-FOS not dissected
  14. 2018 Medium

    AXL was found to bind the TP53 promoter directly (by ChIP) and suppress p53 transcription, revealing a non-canonical nuclear function for a receptor tyrosine kinase.

    Evidence ChIP-qPCR, ChIP-seq, luciferase reporter, and immunofluorescence showing nuclear AXL

    PMID:32992696

    Open questions at the time
    • Mechanism of AXL nuclear translocation not defined
    • Whether AXL binds DNA directly or through a transcription factor complex unknown
    • Not independently replicated
  15. 2018 High

    Axl−/− platelets showed impaired Syk and PLCγ2 phosphorylation upon GPVI stimulation, and AXL blockade inhibited aggregation in a Gas6-independent manner, establishing a ligand-independent scaffolding role for AXL in platelet activation.

    Evidence TAM single-receptor KO mice, platelet aggregation, in vivo thrombosis model, neutralizing antibodies, and recombinant ECD

    PMID:30541554

    Open questions at the time
    • Molecular mechanism of Gas6-independent AXL function in platelets not defined
    • Whether AXL directly interacts with GPVI complex not tested
  16. 2019 High

    Dissection of AXL's dual role in Zika virus infection — mediating entry via Gas6 and suppressing the interferon response via SOCS1/3 upregulation — showed AXL functions both as a viral entry facilitator and an innate immune checkpoint.

    Evidence Receptor/ligand neutralization, kinase inhibition, ISG expression analysis in human Sertoli cells and organoids

    PMID:31311882

    Open questions at the time
    • Whether AXL-dependent SOCS induction is direct or via intermediate kinases not resolved
    • Contribution of other TAM receptors in testis not assessed
  17. 2019 Medium

    PTBP1 was identified as a post-transcriptional regulator that binds AXL mRNA 5′-UTR and decreases its stability, adding an RNA-level control mechanism for AXL expression.

    Evidence RNA-IP, in vitro/in vivo binding assays, mRNA half-life measurements, and xenograft models

    PMID:31729427

    Open questions at the time
    • Exact PTBP1 binding site on AXL 5′-UTR not mapped at nucleotide resolution
    • Whether other RBPs cooperate with PTBP1 not explored
  18. 2020 High

    p85β was shown to stabilize AXL protein by preventing TRIM2/optineurin-mediated autophagic degradation, defining a PI3K-independent scaffolding function for p85β that feeds into AXL-dependent PDK1/SGK3 signaling.

    Evidence Co-IP, siRNA/overexpression, phospho-proteomics, autophagy flux assays, and in vivo tumor models

    PMID:32385243

    Open questions at the time
    • Direct TRIM2 ubiquitination of AXL not demonstrated in vitro
    • Whether this pathway operates outside ovarian cancer not tested
  19. 2020 Medium

    Reconstitution with kinase-dead AXL restored apoE expression in AXL-null astrocytes, demonstrating a kinase-independent scaffolding function for AXL in lipid metabolism.

    Evidence AXL-knockout and kinase-dead reconstitution in human astrocytes with ELISA/Western blot readout

    PMID:32366277

    Open questions at the time
    • Adaptor or scaffold partner mediating AXL kinase-independent apoE regulation not identified
    • In vivo relevance not established
  20. 2022 Medium

    GALNT2-mediated O-glycosylation of AXL was shown to regulate its protein stability through the proteasome, adding glycosylation as another post-translational layer of AXL regulation.

    Evidence GALNT2 overexpression/CRISPR-KO, co-IP, glycan modification assays, and invasion assays

    PMID:36409270

    Open questions at the time
    • Specific O-glycosylation sites on AXL not mapped
    • Relationship to other ubiquitin-dependent degradation pathways (c-Cbl, LZTR1) not clarified
  21. 2023 High

    LZTR1 was identified as the CUL3 adaptor targeting AXL for ubiquitin-dependent lysosomal degradation, and cancer-associated LZTR1 mutations abolished this activity, linking AXL accumulation to oncogenic signaling from loss-of-function LZTR1 mutations.

    Evidence Unbiased biochemical screen, co-IP, genetic mouse models (conditional Lztr1/Cdkn2a KO), ubiquitination assays, and tumor formation

    PMID:36445254

    Open questions at the time
    • Whether LZTR1 and c-Cbl operate on AXL in the same or distinct cellular compartments not resolved
    • Structural basis of LZTR1-AXL recognition unknown
  22. 2023 Medium

    NAT10-dependent ac4C modification of AXL mRNA was shown to increase its stability and drive pancreatic cancer proliferation, adding epitranscriptomic regulation as a mechanism for AXL overexpression.

    Evidence ac4C-seq, mRNA stability assays, NAT10 knockdown/overexpression, and in vivo functional assays

    PMID:37156457

    Open questions at the time
    • Specific ac4C sites on AXL mRNA not mapped at single-nucleotide resolution
    • Whether ac4C modification interacts with PTBP1-mediated mRNA destabilization not examined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How AXL's multiple degradation pathways (c-Cbl, LZTR1-CUL3, TRIM2/optineurin autophagy, GALNT2-proteasome, ectodomain shedding) are coordinated in different cell types, and whether AXL's reported nuclear function in TP53 regulation operates through direct DNA binding or cofactor-mediated recruitment, remain unresolved.
  • Integration of multiple AXL degradation pathways not studied in a single system
  • Mechanism of AXL nuclear translocation uncharacterized
  • Full-length AXL structure with intracellular domain not available

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 3 GO:0140096 catalytic activity, acting on a protein 3 GO:0003677 DNA binding 1
Localization
GO:0005886 plasma membrane 4 GO:0005576 extracellular region 2 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-392499 Metabolism of proteins 4 R-HSA-168256 Immune System 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-109582 Hemostasis 1
Partners
EGFRELMO2GAS6HER3LRP1LZTR1PTBP1RANBP9
Complex memberships
AXL-EGFR/HER3 heterodimerAXL-LRP1-RANBP9 efferocytosis complexGas6-AXL 2:2 signaling complex

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Crystal structure of the Gas6/AXL complex at 3.3 Å resolution reveals a 2:2 stoichiometric assembly in which two immunoglobulin-like domains of the AXL ectodomain are crosslinked by the first laminin G-like domain of Gas6, with no direct AXL/AXL or Gas6/Gas6 contacts. Structure-based mutagenesis and receptor activation experiments demonstrate that both major and minor Gas6-binding sites are required for productive transmembrane signaling. X-ray crystallography, structure-based mutagenesis, protein binding assays, receptor activation experiments The EMBO journal High 16362042
1995 AXL is post-translationally processed by proteolytic cleavage in a 14-amino acid region immediately N-terminal to the transmembrane domain, generating a soluble extracellular domain and a membrane-bound kinase domain. This cleavage is augmented by phorbol ester treatment and does not require protein synthesis or transport. Proteolytic processing enhances receptor turnover at the cell surface, thereby down-regulating AXL kinase activity. Biochemical characterization, phorbol ester stimulation assays, cell surface receptor turnover assays The Journal of biological chemistry High 7822279
2005 Gas6-induced downregulation of AXL is blocked by inhibitors of endocytosis and lysosomal degradation but not by proteasomal inhibitors. Gas6 binding induces AXL phosphorylation, ubiquitination, and interaction with the ubiquitin ligase c-Cbl. Hydrogen peroxide induces AXL tyrosine phosphorylation but not ubiquitination, thereby inhibiting AXL downregulation. In vitro pharmacological inhibition, immunoprecipitation, Western blotting, ubiquitination assays Biochemical and biophysical research communications Medium 15958209
2014 AXL directly phosphorylates Elmo1/2 scaffold proteins on a conserved C-terminal tyrosine residue (Tyr-713 on Elmo2) upon Gas6-dependent activation. Phosphorylated Elmo2 enters a physical complex with AXL and activates Rac1 through Dock family GEFs, promoting breast cancer cell invasion and proliferation. Elmo2 Tyr-713-Phe mutation abolishes these effects. Proteomics, mutagenesis, co-immunoprecipitation, Rac1 activation assays, siRNA knockdown, invasion assays Molecular and cellular biology High 25332238
2014 AXL forms a multiprotein complex with LDL receptor-related protein-1 (LRP-1) and RAN-binding protein 9 (RANBP9) in dendritic cells to mediate efferocytosis and antigen cross-presentation in vivo. AXL binds apoptotic cells but requires LRP-1 to trigger internalization. AXL and LRP-1 do not interact directly but rely on RANBP9 as a bridging adaptor. Targeted genetic deletion in mice, spleen efferocytosis assay, co-immunoprecipitation, antigen cross-presentation coculture assay, in vivo HSV-1 infection model The Journal of clinical investigation High 24509082
2014 An engineered AXL decoy receptor with four mutations in the Gas6-binding interface binds Gas6 with ~80-fold higher affinity than wild-type AXL (femtomolar affinity as Fc fusion), sequesters Gas6, and specifically abrogates AXL signaling. Increased Gas6-binding affinity correlated with inhibition of metastasis in vivo. Rational and combinatorial protein engineering, binding affinity measurements, in vivo tumor/metastasis models Nature chemical biology High 25242553
2010 AXL enhances macropinocytosis of Zaire ebolavirus glycoprotein-dependent entry; RNAi knockdown of AXL reduced ZEBOV entry via macropinocytosis but had no effect on clathrin-dependent or caveola/lipid raft-mediated endocytic pathways. Biochemical inhibitors, RNAi, dominant negative constructs, high-molecular-weight dextran uptake assay, infection assays Journal of virology High 21047970
2019 Axl receptor neutralization and its ligand Gas6 blockade strongly attenuates Zika virus entry in human Sertoli cells, while Axl kinase inhibition (without affecting entry) decreases SOCS1 and SOCS3 levels, increases interferon-stimulated gene expression, and reduces ZIKV replication, demonstrating that Axl negatively regulates the antiviral interferon response in the testis. Receptor/ligand neutralization assays, kinase inhibitor treatment, western blotting, ISG expression analysis, testicular organoid model mBio High 31311882
2003 AXL is active in confluent vascular pericytes via endogenous Gas6 autocrine signaling. Addition of soluble AXL extracellular domain (decoy) inhibited endogenous AXL phosphorylation and enhanced osteogenic differentiation/mineralization, demonstrating that AXL activation suppresses pericyte osteogenic differentiation. Subtractive hybridization, Northern/Western blotting, immunoprecipitation with anti-phosphotyrosine antibody, recombinant protein treatment, nodule mineralization assay Circulation research Medium 12730092
2006 AXL is required for flow-dependent vascular remodeling; Axl-/- mice develop significantly smaller intima+media in response to low-flow carotid ligation, with increased apoptosis (5-fold), decreased p-Akt, and altered vascular cell composition, placing AXL upstream of Akt-mediated survival signaling in VSMC. Axl-/- knockout mouse model, carotid ligation surgery, quantitative immunohistochemistry, apoptosis assays, Western blotting for p-Akt Circulation research High 16627783
2013 Gas6/AXL signaling in schwannoma cells recruits Src, FAK, and NFκB. NFκB mediates Gas6/AXL-driven overexpression of survivin, cyclin D1, and FAK, leading to enhanced cell survival, matrix adhesion, and proliferation. AXL is negatively regulated by merlin and positively regulated by E3 ubiquitin ligase CRL4DCAF1. Gas6 stimulation assays, shRNA knockdown, signaling pathway analysis, cell adhesion and proliferation assays Oncogene Medium 23318455
1993 The human AXL (UFO) receptor is encoded by 20 exons spanning ~44 kb, with alternative splicing of exon 10 and differential polyadenylation generating mRNA isoforms. The promoter is GC-rich, lacks TATA and CAAT boxes, and contains Sp1, AP-2, and CREB binding sites. Genomic library screening, S1 nuclease and primer extension analysis, sequencing Oncogene Medium 8381225
2010 AXL is expressed and activated in mesothelioma cells via autocrine GAS6 signaling; GAS6 knockdown modulates AXL tyrosine phosphorylation. AXL silencing suppresses mesothelioma migration and proliferation via G1 arrest, and AXL inhibition blocks PI3K/AKT/mTOR and RAF/MAPK signaling. Phosphotyrosine immunoaffinity MS, shRNA knockdown, GAS6 modulation, cell cycle analysis, pathway inhibitor studies Oncogene Medium 21132014
2016 AXL dimerizes with EGFR and initiates signaling that circumvents anti-EGFR therapy effects. AXL overexpression and EGFR dimerization can overcome PI3K inhibition by activating the phospholipase C-γ-PKC cascade, which in turn sustains mTORC1 activity. Receptor co-immunoprecipitation, pathway signaling analysis, pharmacological inhibition Clinical cancer research Medium 26763248
2019 Osimertinib stimulates AXL by inhibiting a negative feedback loop. Activated AXL associates with EGFR and HER3 in a complex that maintains cell survival and promotes emergence of osimertinib-tolerant cells. Co-immunoprecipitation, signaling analysis, AXL inhibitor treatment, viability assays, xenograft tumor models Nature communications Medium 30651547
2016 AXL is transcriptionally regulated by AP-1 transcription factors c-JUN and c-FOS; AXL expression correlates with c-JUN, and silencing c-JUN/c-FOS downregulates AXL and restores sensitivity to PI3Kα inhibition. siRNA silencing of c-JUN/c-FOS, qPCR, Western blotting, JNK inhibitor studies, in vivo xenograft models JCI insight Medium 30860495
2019 AXL expression is regulated post-transcriptionally by RNA-binding protein PTBP1, which directly targets the 5'-UTR of AXL mRNA and decreases AXL mRNA stability without affecting transcription rate. RNA-IP, in vitro and in vivo PTBP1-AXL mRNA binding assays, mRNA stability assays, qRT-PCR, tumor xenograft models Scientific reports Medium 31729427
2023 NAT10-mediated N4-acetylcytidine (ac4C) modification of AXL mRNA promotes its stability, leading to increased AXL protein expression and enhanced pancreatic cancer cell proliferation and metastasis. ac4C-seq, mRNA stability assays, NAT10 knockdown/overexpression, in vitro and in vivo functional assays Experimental cell research Medium 37156457
2020 p85β (PIK3R2) prevents autophagic degradation of AXL protein by altering phosphorylation of TRIM2 (an E3 ligase) and optineurin (an autophagy receptor), thereby upregulating AXL protein levels and activating downstream AKT-independent PDK1/SGK3 signaling in ovarian cancer. Co-immunoprecipitation, siRNA/overexpression, phospho-proteomics, autophagy flux assays, in vivo tumor models Nature communications High 32385243
2023 LZTR1 is the substrate-specific adaptor of a CUL3-dependent ubiquitin ligase that targets AXL (and EGFR) for ubiquitin-dependent lysosomal degradation. Pathogenic cancer-associated LZTR1 mutations fail to promote AXL degradation, resulting in AXL protein accumulation and dysregulated signaling. Unbiased biochemical screens, co-immunoprecipitation, genetic mouse models (conditional Lztr1/Cdkn2a knockout), ubiquitination assays, tumor formation assays Cancer discovery High 36445254
2016 Gas6-Axl interaction mediates endothelial uptake of platelet-derived microparticles (PMPs) via Axl on endothelial cells; TAM-blocking antibodies or siRNA knockdown of individual TAMs confirmed Axl and Gas6 as the specific mediators of PMP phagocytosis. Flow cytometry, confocal/electron microscopy, Western blotting, siRNA knockdown, TAM-blocking antibodies, Gas6-/- mouse model The Journal of biological chemistry High 27006397
2018 Protein S (PROS1) secreted by tumor-associated macrophages/microglia activates AXL in mesenchymal glioblastoma stem cells, inducing NFκB activation. PROS1-driven AXL phosphorylation is inhibited by the AXL inhibitor BGB324. Co-immunoprecipitation, phospho-AXL detection, NFκB reporter assays, pharmacological inhibition, in vivo survival studies Cancer research Medium 29531161
2022 Gas6/Axl/Rac1 signaling promotes microglia efferocytosis of apoptotic neurons following subarachnoid hemorrhage; beneficial effects of recombinant Gas6 are abrogated by inhibiting or knocking down Axl or Rac1, placing Rac1 downstream of Axl in this efferocytosis pathway. In vivo mouse SAH model, intraventricular injection, siRNA knockdown, specific inhibitors, in vitro efferocytosis assays Translational stroke research Medium 36324028
2015 AXL is a sensor of local spatial heterogeneity in Gas6 ligand concentration, a property arising from reaction-diffusion interactions. Quantitative experiments and mathematical modeling demonstrate AXL operates distinctly from other RTK families in ligand-sensing mechanism. Quantitative cell-based assays, mathematical/computational modeling, ligand gradient experiments Cell systems Medium 26236777
2020 Axl regulates apolipoprotein E (apoE) homeostasis in human astrocytes; AXL-deficient cells have significantly attenuated apoE expression and secretion, and reconstitution with either wild-type or kinase-dead Axl restores apoE baseline levels, demonstrating a kinase-independent scaffolding role for Axl in apoE regulation. AXL-/- cell line generation, pharmacological Axl inhibition, reconstitution with WT and kinase-dead Axl, ELISA, Western blotting Molecular brain Medium 32366277
2017 YAP transcriptionally regulates AXL expression in EGFR TKI-resistant lung cancer cells; YAP silencing reduces AXL expression, pharmacological or genetic AXL inhibition restores drug sensitivity, placing AXL downstream of YAP in resistance. YAP siRNA/overexpression, ChIP-seq/reporter assay inference, AXL inhibitor treatment, drug sensitivity assays Neoplasia Medium 29136529
2020 Phosphatidylethanolamine (PE) synergizes with phosphatidylserine (PS) to enhance GAS6 recognition, leading to increased AXL-mediated efferocytosis and virus entry. Liposomes containing both PE and PS bound GAS6 and were engulfed by AXL-expressing cells more efficiently than PS alone. Liposome binding assays, AXL-expressing cell efferocytosis assays, virus pseudotype infection assays, flow cytometry Journal of virology Medium 33115868
2018 AXL binds to the initial 600 bp sequence at the 5' end of the TP53 promoter (demonstrated by ChIP-qPCR and sequencing), suppressing TP53 transcription; AXL knockdown induces p53 expression and AXL nuclear colocalization with p53 is observed by immunofluorescence, establishing a feedback regulatory loop. ChIP-qPCR, ChIP-seq, TP53 promoter luciferase assay, qRT-PCR, immunofluorescence, shRNA knockdown Cancers Medium 32992696
2020 AXL mediates cancer cell invasion in esophageal adenocarcinoma through regulation of lysosome peripheral distribution and cathepsin B secretion; this process is mediated by AXL-dependent extracellular acidification through AKT-NFκB-dependent regulation of lactate transporter MCT-1. siRNA knockdown, pharmacological AXL inhibition, lysosome trafficking assays, cathepsin B secretion assays, pH measurements, Western blotting Neoplasia Medium 30189359
2022 GALNT2 modifies O-glycans on AXL and regulates AXL protein levels via the proteasome-dependent pathway; GALNT2-promoted cancer cell invasiveness is significantly reversed by AXL siRNA. GALNT2 overexpression/knockout (CRISPR/Cas9), co-immunoprecipitation, glycan modification assays, AXL protein level analysis, invasion assays Molecular oncology Medium 36409270
2018 Axl and Tyro3, but not Mertk, are required for platelet activation and thrombus formation; Axl-/- platelets show decreased Syk and PLCγ2 tyrosine phosphorylation upon GPVI agonist stimulation; anti-Axl neutralizing antibodies and recombinant Axl extracellular domain inhibit platelet aggregation in a Gas6-independent manner. TAM single-receptor knockout mice, platelet aggregation assays, in vivo laser-induced thrombosis model, phosphorylation analysis, neutralizing antibody and recombinant ECD experiments Cell communication and signaling High 30541554
1999 E1A negatively regulates AXL expression at the transcriptional level; Gas6-triggered AXL signaling counteracts E1A-mediated growth suppression and protects cells from serum deprivation-induced apoptosis, placing AXL as a downstream effector of survival signaling opposing E1A tumor suppression. Degenerate RT-PCR kinase profiling, AXL cDNA transfection, Gas6 stimulation, serum deprivation apoptosis assay Molecular and cellular biology Medium 10567533

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Targeting MET and AXL overcomes resistance to sunitinib therapy in renal cell carcinoma. Oncogene 319 26364599
2019 AXL confers intrinsic resistance to osimertinib and advances the emergence of tolerant cells. Nature communications 289 30651547
2017 Giving AXL the axe: targeting AXL in human malignancy. British journal of cancer 270 28072762
2005 Structural basis for Gas6-Axl signalling. The EMBO journal 238 16362042
2005 Expression of axl in lung adenocarcinoma and correlation with tumor progression. Neoplasia (New York, N.Y.) 224 16354588
1995 UFO: an Arabidopsis gene involved in both floral meristem and floral organ development. The Plant cell 219 7780306
2006 Signalling and functional diversity within the Axl subfamily of receptor tyrosine kinases. Cytokine & growth factor reviews 216 16737840
2011 Targeting Axl and Mer kinases in cancer. Molecular cancer therapeutics 190 21933973
2014 Axl as a mediator of cellular growth and survival. Oncotarget 156 25344858
2005 Multiple roles for the receptor tyrosine kinase axl in tumor formation. Cancer research 156 16230391
1995 The transforming receptor tyrosine kinase, Axl, is post-translationally regulated by proteolytic cleavage. The Journal of biological chemistry 142 7822279
2016 The Receptor Tyrosine Kinase AXL in Cancer Progression. Cancers 131 27834845
2010 The Tyro3 receptor kinase Axl enhances macropinocytosis of Zaire ebolavirus. Journal of virology 131 21047970
2018 Activation of the Receptor Tyrosine Kinase AXL Regulates the Immune Microenvironment in Glioblastoma. Cancer research 123 29531161
2014 An engineered Axl 'decoy receptor' effectively silences the Gas6-Axl signaling axis. Nature chemical biology 123 25242553
2020 Gas6/Axl Signaling Pathway in the Tumor Immune Microenvironment. Cancers 112 32660000
2015 The Axl receptor tyrosine kinase is a discriminator of macrophage function in the inflamed lung. Mucosal immunology 112 25603826
2014 An AXL/LRP-1/RANBP9 complex mediates DC efferocytosis and antigen cross-presentation in vivo. The Journal of clinical investigation 101 24509082
2016 Molecular Pathways: AXL, a Membrane Receptor Mediator of Resistance to Therapy. Clinical cancer research : an official journal of the American Association for Cancer Research 99 26763248
2006 Axl, a receptor tyrosine kinase, mediates flow-induced vascular remodeling. Circulation research 98 16627783
2016 Inhibition of the GAS6/AXL pathway augments the efficacy of chemotherapies. The Journal of clinical investigation 93 27893463
2019 Axl Promotes Zika Virus Entry and Modulates the Antiviral State of Human Sertoli Cells. mBio 84 31311882
2017 YAP-Dependent AXL Overexpression Mediates Resistance to EGFR Inhibitors in NSCLC. Neoplasia (New York, N.Y.) 83 29136529
2003 Receptor tyrosine kinase Axl modulates the osteogenic differentiation of pericytes. Circulation research 83 12730092
2013 Axl/Gas6/NFκB signalling in schwannoma pathological proliferation, adhesion and survival. Oncogene 82 23318455
2023 AXL in cancer: a modulator of drug resistance and therapeutic target. Journal of experimental & clinical cancer research : CR 81 37328828
2018 Cabozantinib: Multi-kinase Inhibitor of MET, AXL, RET, and VEGFR2. Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer 80 30069760
1999 The Gas6/Axl system: a novel regulator of vascular cell function. Trends in cardiovascular medicine 76 11094334
2010 AXL regulates mesothelioma proliferation and invasiveness. Oncogene 75 21132014
2018 BRAF and AXL oncogenes drive RIPK3 expression loss in cancer. PLoS biology 73 30157175
2014 Axl-altered microRNAs regulate tumorigenicity and gefitinib resistance in lung cancer. Cell death & disease 73 24832599
2019 Axl kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas. Molecular cancer 69 30744655
2005 UFO in the Arabidopsis inflorescence apex is required for floral-meristem identity and bract suppression. Planta 69 16244866
2014 Axl phosphorylates Elmo scaffold proteins to promote Rac activation and cell invasion. Molecular and cellular biology 63 25332238
2021 Therapeutic Targeting of the Gas6/Axl Signaling Pathway in Cancer. International journal of molecular sciences 61 34576116
2003 The F-box-containing protein UFO and AGAMOUS participate in antagonistic pathways governing early petal development in Arabidopsis. Proceedings of the National Academy of Sciences of the United States of America 59 12826617
1999 Axl-gas6 interaction counteracts E1A-mediated cell growth suppression and proapoptotic activity. Molecular and cellular biology 56 10567533
2003 Expression of the proto-oncogene Axl in renal cell carcinoma. DNA and cell biology 55 14565870
2019 Repression of AXL expression by AP-1/JNK blockage overcomes resistance to PI3Ka therapy. JCI insight 53 30860495
1998 Determinants for transformation induced by the Axl receptor tyrosine kinase. Oncogene 53 9671397
2005 Effects of Gas6 and hydrogen peroxide in Axl ubiquitination and downregulation. Biochemical and biophysical research communications 51 15958209
2016 Androgen receptor promotes melanoma metastasis via altering the miRNA-539-3p/USP13/MITF/AXL signals. Oncogene 49 27869170
2025 AXL signaling in cancer: from molecular insights to targeted therapies. Signal transduction and targeted therapy 48 39924521
2022 The Development of AXL Inhibitors in Lung Cancer: Recent Progress and Challenges. Frontiers in oncology 47 35311091
2018 Engineering Axl specific CAR and SynNotch receptor for cancer therapy. Scientific reports 47 29497107
2018 MERTK Mediates Intrinsic and Adaptive Resistance to AXL-targeting Agents. Molecular cancer therapeutics 47 30093568
2016 The Gas6-Axl Protein Interaction Mediates Endothelial Uptake of Platelet Microparticles. The Journal of biological chemistry 46 27006397
2014 AXL receptor tyrosine kinase is increased in patients with heart failure. International journal of cardiology 45 24681018
2018 AXL Is a Putative Tumor Suppressor and Dormancy Regulator in Prostate Cancer. Molecular cancer research : MCR 44 30291220
2015 The AXL Receptor is a Sensor of Ligand Spatial Heterogeneity. Cell systems 43 26236777
2023 AXL Inhibitors: Status of Clinical Development. Current oncology reports 42 36920638
2022 Gas6 Promotes Microglia Efferocytosis and Suppresses Inflammation Through Activating Axl/Rac1 Signaling in Subarachnoid Hemorrhage Mice. Translational stroke research 41 36324028
2007 S-Nitrosylation and uncompetitive/fast off-rate (UFO) drug therapy in neurodegenerative disorders of protein misfolding. Cell death and differentiation 41 17431424
2021 AXL Receptor in Cancer Metastasis and Drug Resistance: When Normal Functions Go Askew. Cancers 40 34638349
2015 AXL receptor tyrosine kinase as a therapeutic target in NSCLC. Lung Cancer (Auckland, N.Z.) 40 28210148
2020 Soluble AXL as a marker of disease progression and survival in melanoma. PloS one 38 31917795
2019 PTBP1-mediated regulation of AXL mRNA stability plays a role in lung tumorigenesis. Scientific reports 38 31729427
2023 NAT10-mediated AXL mRNA N4-acetylcytidine modification promotes pancreatic carcinoma progression. Experimental cell research 36 37156457
2020 Therapeutic aspects of the Axl/Gas6 molecular system. Drug discovery today 36 33002607
2021 Immune Evasion Mechanism and AXL. Frontiers in oncology 35 34778071
2016 Impact of Expression of Vimentin and Axl in Breast Cancer. Clinical breast cancer 35 27506606
2013 Axl gene knockdown inhibits the metastasis properties of hepatocellular carcinoma via PI3K/Akt-PAK1 signal pathway. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 35 24347489
2023 The F-box protein UFO controls flower development by redirecting the master transcription factor LEAFY to new cis-elements. Nature plants 34 36732360
2023 Gas6/AXL pathway: immunological landscape and therapeutic potential. Frontiers in oncology 33 37265798
2020 Differential regulation of hepatic physiology and injury by the TAM receptors Axl and Mer. Life science alliance 33 32571802
2017 Protein S drives oral squamous cell carcinoma tumorigenicity through regulation of AXL. Oncotarget 33 28118606
2020 Phosphatidylethanolamine and Phosphatidylserine Synergize To Enhance GAS6/AXL-Mediated Virus Infection and Efferocytosis. Journal of virology 32 33115868
1997 Recent progress on the role of Axl, a receptor tyrosine kinase, in malignant transformation of myeloid leukemias. Leukemia & lymphoma 31 9130617
2020 Testosterone ameliorates vascular aging via the Gas6/Axl signaling pathway. Aging 30 32717722
2017 Phenotypic screening identifies Axl kinase as a negative regulator of an alveolar epithelial cell phenotype. Laboratory investigation; a journal of technical methods and pathology 30 28553934
2016 Sunitinib activates Axl signaling in renal cell cancer. International journal of cancer 30 26815723
2016 Gene of the month: Axl. Journal of clinical pathology 30 26951083
2015 AXL is a potential therapeutic target in dedifferentiated and pleomorphic liposarcomas. BMC cancer 29 26573603
1993 The genomic structure of the human UFO receptor. Oncogene 28 8381225
2021 AXL Is a Key Factor for Cell Plasticity and Promotes Metastasis in Pancreatic Cancer. Molecular cancer research : MCR 27 33811159
2020 p85β regulates autophagic degradation of AXL to activate oncogenic signaling. Nature communications 27 32385243
2018 Dynamics of Axl Receptor Shedding in Hepatocellular Carcinoma and Its Implication for Theranostics. International journal of molecular sciences 27 30567378
2020 AXL Receptor in Breast Cancer: Molecular Involvement and Therapeutic Limitations. International journal of molecular sciences 26 33182542
2017 LncRNA-MALAT1-mediated Axl promotes cell invasion and migration in human neuroblastoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 26 28468579
2017 Luteolin inhibits angiogenesis by blocking Gas6/Axl signaling pathway. International journal of oncology 25 28627676
2018 AXL Mediates Esophageal Adenocarcinoma Cell Invasion through Regulation of Extracellular Acidification and Lysosome Trafficking. Neoplasia (New York, N.Y.) 24 30189359
2021 Targeting AXL in NSCLC. Lung Cancer (Auckland, N.Z.) 23 34408519
2020 Axl-148b chimeric aptamers inhibit breast cancer and melanoma progression. International journal of biological sciences 23 32174798
2013 An activated form of UFO alters leaf development and produces ectopic floral and inflorescence meristems. PloS one 23 24376756
2019 A novel human anti-AXL monoclonal antibody attenuates tumour cell migration. Scandinavian journal of immunology 22 31075180
2018 Tyro3, Axl, and Mertk receptors differentially participate in platelet activation and thrombus formation. Cell communication and signaling : CCS 22 30541554
2015 AXL as a modulator of sunitinib response in glioblastoma cell lines. Experimental cell research 22 25637219
2019 Quinolone antibiotic derivatives as new selective Axl kinase inhibitors. European journal of medicinal chemistry 21 30731400
2022 GALNT2 promotes invasiveness of colorectal cancer cells partly through AXL. Molecular oncology 20 36409270
2020 MicroRNA 34a-AXL Axis Regulates Vasculogenic Mimicry Formation in Breast Cancer Cells. Genes 20 33374832
2019 Mechanism of gut microbiota and Axl/SOCS3 in experimental autoimmune encephalomyelitis. Bioscience reports 20 31221818
2017 Epigenetic regulation of AXL and risk of childhood asthma symptoms. Clinical epigenetics 20 29177020
2016 Role of AXL expression in non-small cell lung cancer. Oncology letters 20 28105215
2021 Targeting the AXL Receptor in Combating Smoking-related Pulmonary Fibrosis. American journal of respiratory cell and molecular biology 19 33730527
2019 Unknown fates of (brain) oxidation or UFO: Close encounters with neuronal senescence. Free radical biology & medicine 19 30639615
2019 Macrophage phenotypes and Gas6/Axl signaling in apical lesions. Journal of dental sciences 19 31528256
2023 LZTR1 Mutation Mediates Oncogenesis through Stabilization of EGFR and AXL. Cancer discovery 18 36445254
2021 AXL, an Important Host Factor for DENV and ZIKV Replication. Frontiers in cellular and infection microbiology 18 33954117
2020 Axl receptor tyrosine kinase is a regulator of apolipoprotein E. Molecular brain 17 32366277
2020 AXL Inactivation Inhibits Mesothelioma Growth and Migration via Regulation of p53 Expression. Cancers 17 32992696