Affinage

GAS6

Growth arrest-specific protein 6 · UniProt Q14393

Length
678 aa
Mass
74.9 kDa
Annotated
2026-06-10
100 papers in source corpus 39 papers cited in narrative 39 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

GAS6 is a secreted, vitamin K-dependent ligand for the TAM receptor tyrosine kinase family (AXL, TYRO3, MERTK) that bridges phosphatidylserine-exposing membranes to TAM receptors to control efferocytosis, cell survival, proliferation, platelet activation, and inflammation (PMID:15184064, PMID:16564713, PMID:29304470). Structurally, GAS6 assembles a 2:2 complex with AXL in which its first laminin G-like domain crosslinks the two immunoglobulin-like domains of the AXL ectodomain through both a major and a minor binding site, both required for productive transmembrane signaling (PMID:16362042). GAS6 biological activity depends on vitamin K-dependent gamma-carboxylation of its N-terminal Gla residues: warfarin-treated GAS6 lacking this modification fails to activate AXL or stimulate proliferation (PMID:15184064), and phosphatidylethanolamine synergizes with phosphatidylserine to maximize GAS6-mediated membrane recognition and engulfment (PMID:33115868). Through TAM receptor engagement GAS6 triggers PI3K/AKT, ERK/MAPK, STAT3, RAC1, and NF-κB signaling cascades that converge on cell survival, mitogenesis, actin remodeling and invasion, and transcriptional programs (PMID:11546821, PMID:15605394, PMID:34244439, PMID:23318455). In platelets GAS6 acts as a response amplifier, reinforcing outside-in αIIbβ3 integrin signaling through all three TAM receptors to drive thrombus stabilization without affecting baseline hemostasis (PMID:11175853, PMID:16564713). In the immune and tissue-repair setting GAS6 is induced as a STAT6-driven macrophage program that mediates efferocytosis of apoptotic cells and dampens NF-κB-dependent inflammatory cytokine output (PMID:20103767, PMID:31363052), while in pathology GAS6/AXL signaling from stromal and recruited myeloid cells promotes tumor proliferation, invasion, and metastatic regrowth (PMID:30531835, PMID:35022267). In circulation, essentially all GAS6 is sequestered in complex with soluble AXL, providing a mechanism for tight control of its bioavailability (PMID:20088931).

Mechanistic history

Synthesis pass · year-by-year structured walk · 37 steps
  1. 1997 High

    Established that GAS6 can act as a cell-surface bridging molecule, engaging AXL on adjacent cells to drive heterotypic adhesion through domains distinct from receptor activation, independent of AXL kinase activity.

    Evidence Cell aggregation assays in AXL-expressing 32D cells with soluble AXL blockade, kinase-dead AXL, and domain mapping

    PMID:9287338

    Open questions at the time
    • Did not resolve which GAS6 domain mediates cell-surface binding at residue level
    • Physiological relevance of kinase-independent adhesion not established in vivo
  2. 1999 Medium

    Placed GAS6/AXL signaling downstream of E1A tumor-suppressive control of survival and mitogenesis, linking the ligand to apoptosis protection.

    Evidence E1A-expressing cells with AXL re-expression, GAS6 treatment, apoptosis/proliferation assays, RT-PCR

    PMID:10567533

    Open questions at the time
    • Single-cell-system epistasis
    • Downstream survival effectors not mapped
  3. 2001 High

    Defined GAS6 as a non-redundant amplifier of platelet activation, revealing its therapeutic potential as an antithrombotic target that spares hemostasis.

    Evidence Gas6 knockout mice, venous/arterial thrombosis models, platelet aggregation assays, anti-Gas6 antibody inhibition

    PMID:11175853

    Open questions at the time
    • Did not assign the responsible platelet TAM receptor
    • Molecular link to integrin signaling not yet defined
  4. 2001 High

    Identified the GAS6/AXL→STAT3 axis as a driver of mesangial cell proliferation, and showed gamma-carboxylation-dependent activity is targetable in vivo with warfarin or soluble AXL decoy.

    Evidence Mesangial STAT3 phosphorylation, dominant-negative STAT3, warfarin and AXL-Fc inhibition in rat Thy1 glomerulonephritis

    PMID:11290560 PMID:11546821

    Open questions at the time
    • Connection between STAT3 and PDGF-B induction not fully resolved
    • Receptor-proximal signaling steps to STAT3 unmapped
  5. 2001 Medium

    Connected GAS6 signaling to beta-catenin/TCF transcriptional activation through PI3K/AKT-mediated GSK3 inhibition, extending its mitogenic reach to Wnt-effector control.

    Evidence PI3K/AKT/GSK3 assays, wortmannin epistasis, beta-catenin fractionation, TCF reporter in C57MG cells

    PMID:11154277

    Open questions at the time
    • Receptor mediating the effect not specified
    • Single cell line, pharmacological inhibitor-based
  6. 2004 High

    Demonstrated that vitamin K-dependent gamma-carboxylation of GAS6 is strictly required for AXL activation and biological function, establishing a post-translational gate on ligand activity.

    Evidence Matched active vs warfarin-treated recombinant GAS6, cardiac fibroblast assays, AXL/ERK phosphorylation, AXL-Fc blockade

    PMID:15184064

    Open questions at the time
    • Structural basis of Gla-domain membrane tethering not resolved here
    • Relative contribution of carboxylation to receptor vs membrane binding unclear
  7. 2004 Medium

    Extended GAS6/AXL anti-apoptotic survival signaling via AKT to additional epithelial contexts (lens), reinforcing a general survival role.

    Evidence AXL/AKT phosphorylation, viability and caspase-3 assays in human lens epithelial cells

    PMID:14667825

    Open questions at the time
    • Single lab/cell type
    • In vivo relevance not tested
  8. 2005 High

    Solved the GAS6/AXL complex structure, defining the 2:2 architecture and the dual-site binding requirement that underlies receptor crosslinking and activation.

    Evidence X-ray crystallography (3.3 Å), structure-based mutagenesis, receptor activation assays

    PMID:16362042

    Open questions at the time
    • Structure of GAS6 Gla domain engaging membrane PS not captured
    • Complexes with TYRO3 and MERTK not structurally defined
  9. 2005 Medium

    Mapped the GAS6/AXL mitogenic output to MEK/ERK (not AKT) in prostate carcinoma, separating proliferative from survival signaling branches.

    Evidence Proliferation assays, AKT/MAPK immunoblots, MEK inhibitor epistasis in PC-3 and DU145 cells

    PMID:15605394

    Open questions at the time
    • Single lab pharmacological epistasis
    • In vivo tumor relevance not addressed here
  10. 2005 Medium

    Identified an autocrine/paracrine GAS6/AXL survival role in hepatic oval cells during liver regeneration, distinguishing anti-apoptotic from mitogenic activity.

    Evidence Partial hepatectomy/AAF rat model, immunohistochemistry, GAS6 treatment of WB-F344 cells, apoptosis assays

    PMID:16285961

    Open questions at the time
    • Downstream survival pathway not delineated
    • Direct in vivo causality from GAS6 loss not tested
  11. 2005 High

    Showed all three TAM receptors are expressed on platelets and individually required, defining the receptor basis for GAS6 thrombotic amplification.

    Evidence Flow cytometry, receptor-specific blocking antibodies, platelet aggregation/degranulation, mouse thrombosis vs clopidogrel

    PMID:15733062

    Open questions at the time
    • Mechanism by which three receptors cooperate not resolved
    • Quantitative contribution of each receptor unclear
  12. 2006 High

    Established the mechanistic link between GAS6/TAM signaling and outside-in αIIbβ3 integrin signaling via PI3K/AKT and β3 phosphorylation, explaining clot retraction and second-wave aggregation defects.

    Evidence Tyro3-/-, Axl-/-, Mer-/- mice, aggregation/clot retraction assays, integrin signaling analysis

    PMID:16564713

    Open questions at the time
    • Whether receptors act in cis or trans on platelets unresolved
    • Source of platelet GAS6 not defined here
  13. 2008 High

    Revealed GAS6 as an Epo-induced amplifier of erythroblast survival via AKT, expanding its role to stress erythropoiesis.

    Evidence Gas6 knockout mice, Epo stimulation, AKT immunoblot, hematocrit measurement, GAS6 rescue

    PMID:18188450

    Open questions at the time
    • Receptor mediating erythroblast effect not specified
    • Mechanism of Epo-induced GAS6 release unclear
  14. 2008 Medium

    Showed extracellular glucose reprograms GAS6/AXL output by switching AXL binding partners (p85-PI3K vs SHP-2), demonstrating context-dependent pathway selection.

    Evidence Co-IP of AXL with p85 or SHP-2, AKT/mTOR/ERK immunoblots, apoptosis and migration assays under varying glucose

    PMID:18292389

    Open questions at the time
    • Mechanism linking glucose to partner switching unknown
    • Single lab, VSMC-restricted
  15. 2010 Medium

    Defined a MERTK-specific anti-inflammatory arm of GAS6 signaling that suppresses NF-κB via AKT/GSK3β, linking the ligand to cytokine restraint.

    Evidence Cytokine ELISA, TAM receptor immunoblots, AKT/GSK3β/NF-κB assays in U937 cells and macrophages

    PMID:20103767

    Open questions at the time
    • Single TAM-expressing cell model
    • Generality across macrophage subsets not tested
  16. 2010 High

    Discovered that circulating GAS6 is fully sequestered by soluble AXL, providing a bioavailability-control mechanism that limits membrane TAM activation.

    Evidence ELISA, gel filtration, immunoprecipitation of human serum for GAS6/sAXL complexes

    PMID:20088931

    Open questions at the time
    • Regulation of sAXL shedding not addressed
    • Functional consequence of altering the GAS6/sAXL set point untested
  17. 2013 Medium

    Mapped GAS6/AXL pro-survival/adhesion signaling in schwannoma to a Src/FAK/NF-κB module driving survivin, cyclin D1, and FAK expression.

    Evidence Primary schwannoma cells, pathway inhibition, siRNA, survival and adhesion assays

    PMID:23318455

    Open questions at the time
    • Single lab/tumor type
    • Direct vs indirect transcriptional regulation not resolved
  18. 2014 High

    Showed GAS6/AXL induces endothelial tissue factor by signaling within caveolin-1 lipid raft microdomains, defining a spatial requirement and a c-Src→AKT hierarchy.

    Evidence siRNA (AXL, caveolin-1, c-Src, AKT), lipid raft fractionation, confocal microscopy, tissue factor readouts

    PMID:24354620

    Open questions at the time
    • How GAS6 directs AXL to rafts unknown
    • Single lab
  19. 2016 Medium

    Identified GAS6/AXL as the mechanism for endothelial uptake of platelet microparticles, and reconfirmed AXL specificity over MERTK/TYRO3 in serum.

    Evidence Labeled PMP uptake, TAM-blocking antibodies and siRNA, microscopy in endothelial cells

    PMID:27006397

    Open questions at the time
    • Physiological consequence of PMP clearance not defined
    • Single lab
  20. 2016 Medium

    Extended GAS6 to a pro-myelinating/oligodendrocyte function acting through TYRO3 and STAT3, with downregulation of MMP9.

    Evidence Optic nerve and cerebellar slice cultures, MBP immunostaining, STAT3/TYRO3 phosphorylation, TYRO3 knockdown

    PMID:27630207

    Open questions at the time
    • In vivo remyelination not tested here
    • Direct vs indirect effect on oligodendrocytes unclear
  21. 2016 Medium

    Used an ultrahigh-affinity AXL decoy to reveal that GAS6/AXL signaling supports the DNA damage response and homologous recombination.

    Evidence Engineered decoy MYD1-72, γH2AX/53BP1/RAD51 focus assays, in vitro and in vivo cancer models

    PMID:27893463

    Open questions at the time
    • Molecular link between AXL signaling and HR machinery not defined
    • Single lab
  22. 2017 High

    Identified a GAS6-driven inflammatory monocyte recruitment program in venous thrombosis acting via endothelial CCL2/monocyte CCR2 and JNK signaling.

    Evidence Gas6 KO mice, flow cytometry, monocyte/CCR2/CCL2 depletion, JNK inhibition, DVT models

    PMID:28450294

    Open questions at the time
    • Receptor mediating endothelial CCL2 induction not specified
    • Direct GAS6 target cell for chemokine induction unresolved
  23. 2018 Medium

    Demonstrated a paracrine macrophage-GAS6→AXL→AKT/STAT3 circuit driving premalignant mammary progression, linking stromal GAS6 to early tumorigenesis.

    Evidence 3D macrophage/premalignant co-culture, stromal Gas6-/- mice, AKT/STAT3 immunoblot, in vivo tumor assays

    PMID:30531835

    Open questions at the time
    • Trigger for macrophage GAS6 production not defined here
    • Single model system
  24. 2018 Medium

    Showed GAS6 (with protein S) bridges PS on HIV-1-infected cells to macrophage MERTK to mediate their efferocytic clearance, illustrating the PS-bridge mechanism in infection.

    Evidence Phagocytosis assays with recombinant GAS6/protein S, MER-blocking antibodies, PS measurement

    PMID:29304470

    Open questions at the time
    • In vivo relevance to HIV clearance not established
    • Single lab
  25. 2019 High

    Identified STAT6 as the transcriptional writer of macrophage GAS6 during phenotypic transition and showed GAS6+ macrophages resolve inflammation by clearing apoptotic neutrophils.

    Evidence IL-4/TSG6 priming, STAT6 inhibition, Gas6 siRNA, adoptive transfer in murine acute lung injury

    PMID:31363052

    Open questions at the time
    • Receptor on phagocyte mediating clearance not specified here
    • STAT6-GAS6 promoter interaction not directly mapped
  26. 2019 Medium

    Placed GAS6 upstream of MTOR in regulating mitophagy during oocyte maturation, extending its function to organelle quality control.

    Evidence Gas6 siRNA in oocytes, RNA-seq, MTOR immunoblot, rapamycin rescue, mtDNA quantification

    PMID:31316104

    Open questions at the time
    • Receptor/signaling linking GAS6 to MTOR unknown
    • Single lab
  27. 2020 Medium

    Defined the membrane lipid requirement for GAS6 recognition, showing phosphatidylethanolamine synergizes with phosphatidylserine to maximize engulfment and viral entry.

    Evidence Liposome binding, GAS6-PS binding, AXL-cell efferocytosis, pseudovirus inhibition assays

    PMID:33115868

    Open questions at the time
    • Structural basis of PE synergy not resolved
    • In vivo relevance untested
  28. 2020 Medium

    Showed GAS6 promotes microglial efferocytosis of apoptotic neurons after subarachnoid hemorrhage via AXL/RAC1, reducing neuroinflammation.

    Evidence Mouse SAH model, rGAS6 injection, AXL/RAC1 siRNA/inhibitors, efferocytosis and neurological assays

    PMID:36324028

    Open questions at the time
    • Single model
    • Relative roles of efferocytosis vs direct neuroprotection not separated
  29. 2020 Medium

    Demonstrated redundancy among TAM receptors for GAS6 anti-inflammatory signaling in microglia, where either AXL or MERTK alone suffices to suppress TNF-α.

    Evidence Primary microglia from WT, Axl-/-, Mer-/- mice, LPS stimulation, GAS6 pretreatment, TNF-α readouts

    PMID:33192322

    Open questions at the time
    • Downstream signaling not mapped here
    • Single lab
  30. 2020 Medium

    Linked GAS6 anti-inflammatory cytokine induction (IL-10/TGF-β, requiring AXL and TYRO3) to its pro-myelinating action through IL-10.

    Evidence Axl-/- and Tyro3-/- glial cultures, GAS6 treatment, IL-10/TGF-β qPCR, IL-10 neutralization, MBP staining

    PMID:32722558

    Open questions at the time
    • Cell source of cytokines within mixed cultures unclear
    • In vivo confirmation lacking
  31. 2021 High

    Resolved the actin-remodeling output of GAS6/AXL, linking AXL kinase activity through PI3K and RAC1 to membrane ruffling, macropinocytosis-driven receptor internalization, and cancer cell invasion.

    Evidence AXL interactome, live actin imaging, macropinocytosis assays, kinase-dead AXL, PI3K/RAC1 inhibitors, 3D invasion

    PMID:34244439

    Open questions at the time
    • Specific interactome members mediating actin dynamics not all validated
    • Single lab
  32. 2021 High

    Placed GAS6 in a stress-responsive stem cell niche circuit, where corticosterone-mediated GAS6 suppression in dermal papilla enforces hair follicle stem cell quiescence.

    Evidence Adrenalectomy, chronic stress models, niche-specific GAS6 restoration, HFSC activation quantification in mice

    PMID:33790465

    Open questions at the time
    • Receptor/signaling in HFSCs not specified here
    • Direct vs indirect GAS6 action on stem cells unresolved
  33. 2022 High

    Identified neutrophil-derived GAS6 as a driver of chemotherapy-resistant pancreatic cancer liver metastasis via AXL on tumor cells, validated in patient-derived explants.

    Evidence Cytometry, mouse PDAC metastasis models, GAS6/AXL inhibition, patient-derived liver explants, recombinant GAS6

    PMID:35022267

    Open questions at the time
    • Trigger for neutrophil GAS6 induction post-chemotherapy unclear
    • Downstream tumor-intrinsic effectors not fully mapped
  34. 2023 Medium

    Identified PRAME as a direct transcriptional target of GAS6/AXL/MAPK-ERK1/2 in hepatocellular carcinoma promoting migration and invasion.

    Evidence RNA-seq of matched AXL+/AXL- HCC cells, AXL and MEK/ERK inhibition, PRAME gain/loss-of-function, patient analysis

    PMID:37173882

    Open questions at the time
    • Direct promoter occupancy by ERK-driven factors not shown
    • Single lab
  35. 2023 Medium

    Linked GAS6 cardioprotection in sepsis to suppression of the NLRP3 inflammasome, defining NLRP3 as a downstream effector.

    Evidence AAV9-GAS6 overexpression and GAS6 KO mice, CLP sepsis, NLRP3/mitochondrial/apoptosis assays, scRNA-seq

    PMID:37979891

    Open questions at the time
    • Receptor and proximal signaling to NLRP3 not defined
    • Single lab
  36. 2024 Medium

    Showed MSC-EV-delivered GAS6 enhances macrophage efferocytosis via MERTK/ERK/COX2 to limit hepatic ischemia-reperfusion injury.

    Evidence MSC-EV proteomics, GAS6 lentiviral knockdown, MERTK inhibitor UNC2025, efferocytosis assays, murine HIRI model

    PMID:39256347

    Open questions at the time
    • Mechanism of GAS6 EV enrichment unclear
    • Single lab
  37. 2024 Medium

    Established that GAS6/AXL inhibits ferroptosis during hepatic ischemia-reperfusion through PI3K/AKT, reducing lipid peroxidation and iron accumulation.

    Evidence Mouse liver I/R and hepatocyte H/R, recombinant GAS6, AXL inhibitor R428, PI3K inhibitor LY294002, ferroptosis assays

    PMID:38725107

    Open questions at the time
    • Molecular link between AKT and ferroptosis machinery not resolved
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How GAS6 bioavailability set by the soluble AXL reservoir is dynamically regulated to license context-specific TAM receptor signaling across tissues remains unresolved.
  • No mechanism for regulated release of GAS6 from sAXL complexes
  • Determinants of which TAM receptor is engaged in vivo not defined
  • Structures of GAS6 with TYRO3 and MERTK not solved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0060089 molecular transducer activity 3 GO:0008289 lipid binding 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005576 extracellular region 3 GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-109582 Hemostasis 3 R-HSA-1643685 Disease 3
Partners
AXLMERTKPROS1TYRO3
Complex memberships
GAS6-AXL 2:2 signaling complexGAS6-soluble AXL serum complex

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Crystal structure of the human Gas6/Axl complex at 3.3 Å resolution reveals a 2:2 stoichiometric assembly in which the 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 a major and a minor Gas6/Axl binding site are required for productive transmembrane signaling. X-ray crystallography (3.3 Å), structure-based mutagenesis, protein binding assays, receptor activation experiments The EMBO journal High 16362042
2001 Gas6 deficiency in mice prevents venous and arterial thrombosis and protects against fatal collagen/epinephrine-induced thromboembolism without causing spontaneous bleeding. Gas6 amplifies platelet aggregation and secretion in response to known agonists, functioning as a platelet-response amplifier. Gas6 knockout mice, thrombosis models (venous/arterial), platelet aggregation assays, anti-Gas6 antibody inhibition in vitro and in vivo Nature medicine High 11175853
1997 GAS6 mediates cell-cell adhesion via a heterotypic intercellular mechanism: cell-surface-bound GAS6 engages the Axl receptor on an adjacent cell, causing aggregation of Axl-expressing cells. Cell surface binding of GAS6 maps to domains distinct from the Axl-receptor-binding motifs, and Axl kinase activity is not required for aggregation. Cell aggregation assays in 32D myeloid cells expressing Axl, blocking with soluble Axl ectodomain, kinase-dead Axl constructs, binding domain mapping The Journal of biological chemistry High 9287338
2001 Gas6 induces mesangial cell proliferation through Axl by tyrosine-phosphorylating and activating the latent transcription factor STAT3, causing its nuclear translocation. Dominant-negative STAT3 abolishes Gas6-induced proliferation. In a rat mesangial proliferative glomerulonephritis model, warfarin or soluble Axl ectodomain (Axl-Fc) block STAT3 phosphorylation in vivo. In vitro mesangial cell STAT3 phosphorylation assays, dominant-negative STAT3 transfection, warfarin and Axl-Fc inhibition in vivo (Thy1 glomerulonephritis model) The Journal of biological chemistry High 11546821
2001 In experimental mesangial proliferative glomerulonephritis (Thy1 GN), Gas6 and Axl expression are markedly upregulated in glomeruli in parallel with disease progression. Warfarin (which blocks Gas6 gamma-carboxylation/activation) or soluble Axl-Fc fusion protein inhibit mesangial cell proliferation and abolish PDGF-B induction in vivo, demonstrating that the Gas6/Axl pathway drives mesangial proliferation. Warfarin treatment and Axl-Fc injection in rat Thy1 glomerulonephritis model, mRNA/protein quantification The American journal of pathology High 11290560
2004 Recombinant Gas6 containing N-terminal gamma-carboxyglutamic acid residues (vitamin K-dependent modification) stimulates cardiac fibroblast proliferation, DNA synthesis, survival under serum starvation, and activates Axl tyrosine phosphorylation and ERK kinase. Warfarin-treated Gas6 (lacking gamma-carboxylation) neither activates Axl nor stimulates fibroblast proliferation, demonstrating that vitamin K-dependent gamma-carboxylation is required for Gas6 biological activity. In vitro cardiac fibroblast proliferation/DNA synthesis assays from Gas6-/- mice, anti-Gas6 antibody and soluble Axl-Fc inhibition, warfarin-treated recombinant Gas6, Axl phosphorylation immunoblot, ERK phosphorylation Biochemical and biophysical research communications High 15184064
2005 Gas6/Axl interaction in prostate carcinoma cell lines (PC-3, DU145) induces proliferation proportional to Axl expression level. Gas6-stimulated Axl activates AKT and MAPK phosphorylation, and MEK (but not AKT) phosphorylation is essential for the mitogenic effect. Cell proliferation assays, AKT/MAPK phosphorylation immunoblots, MEK inhibitor epistasis in PC-3 and DU145 cells Journal of cellular physiology Medium 15605394
2010 GAS6 inhibits LPS-induced TNF-α and IL-6 secretion by monocytes/macrophages through Mer (not Axl or Tyro3), which is the only TAM receptor expressed on differentiated U937 cells. Mer activation by GAS6 leads to increased Akt phosphorylation, GSK3β phosphorylation, and consequent inhibition of NF-κB nuclear translocation. Cytokine ELISA, immunoblotting for Mer/Axl/Tyro3, Akt/GSK3β/NF-κB phosphorylation assays, differentiated U937 cells and primary macrophages Journal of leukocyte biology Medium 20103767
2010 In human blood, all circulating Gas6 is complexed with soluble Axl (sAxl) at ~0.6 nM concentration; no complexes between Gas6 and soluble Mer or Tyro3 are detected. This suggests that circulating Gas6 is sequestered by sAxl and thereby inhibited from stimulating membrane TAM receptors. ELISA for Gas6, sAxl, and sAxl-Gas6 complexes; gel filtration fractionation; immunoprecipitation of serum Journal of thrombosis and haemostasis : JTH High 20088931
2005 Gas6 receptors Axl, Sky (Tyro3), and Mer are all present on both human and mouse platelets. Anti-Gas6 antibody or blocking antibodies to Sky or Mer inhibit platelet aggregation and degranulation by >80%. A stimulatory anti-Axl antibody increases platelet activation. Gas6 or Sky blocking antibodies reduce thrombus weight in mice similarly to clopidogrel but without increased bleeding. Flow cytometry for receptor expression, platelet aggregation/degranulation assays with blocking antibodies, mouse thrombosis model, clopidogrel comparison Journal of thrombosis and haemostasis : JTH High 15733062
2006 Gas6 amplifies platelet activation through all three TAM receptors (Tyro3, Axl, Mer), reinforcing outside-in αIIbβ3 integrin signaling via PI3K/Akt and tyrosine phosphorylation of the β3 integrin subunit. Loss of any single Gas6 receptor in mice protects against thromboembolism and impairs second-wave platelet aggregation and clot retraction. Single-receptor knockout mice (Tyro3-/-, Axl-/-, Mer-/-), platelet aggregation/clot retraction assays, αIIbβ3 signaling analysis, thromboembolism models Blood cells, molecules & diseases High 16564713
2008 Murine erythroblasts release Gas6 in response to erythropoietin (Epo), and Gas6 enhances Epo receptor signaling by activating Akt (serine-threonine kinase) in erythroblasts. In Gas6-/- mice, erythroid progenitors are hyporesponsive to Epo survival activity and fail to restore hematocrit after anemia. Administration of Gas6 normalizes hematocrit in acute anemia and synergizes with Epo in a chronic anemia model. Gas6 knockout mice, Epo stimulation assays, Akt phosphorylation immunoblot, hematocrit measurements, Gas6 administration experiments The Journal of clinical investigation High 18188450
2019 STAT6 transcription factor, activated downstream of IL-4 or TSG6 signaling, drives Gas6 expression in macrophages during phenotypic transition. Gas6-expressing macrophages mediate efferocytosis of apoptotic neutrophils to resolve inflammatory lung injury. Adoptive transfer of Gas6-depleted macrophages fails to clear apoptotic neutrophils in LPS-challenged mice. IL-4/TSG6 priming of bone marrow macrophages, STAT6 inhibition, Gas6 siRNA depletion, adoptive transfer experiments in murine LPS-induced acute lung injury model Proceedings of the National Academy of Sciences of the United States of America High 31363052
2021 Corticosterone acts on dermal papilla cells to suppress Gas6 expression, which maintains hair follicle stem cell (HFSC) quiescence. Restoring Gas6 expression in dermal papilla overcomes stress-induced HFSC quiescence and drives hair follicle re-entry into regeneration cycles. Adrenalectomy (corticosterone removal), chronic stress models, Gas6 conditional restoration in dermal papilla, HFSC activation quantification in mice Nature High 33790465
2021 GAS6-mediated AXL activation triggers actin remodeling manifested as peripheral membrane ruffling and circular dorsal ruffles (CDRs), promoting macropinocytosis (which internalizes GAS6-AXL complexes), focal adhesion turnover, cell spreading/elongation, and cancer cell invasion. These effects require AXL kinase activity (not TYRO3) and downstream activation of PI3K and RAC1. AXL interactome (co-IP/MS), live imaging of actin dynamics, macropinocytosis assays, kinase-dead AXL mutants, PI3K and RAC1 inhibitors, 3D spheroid invasion assays Proceedings of the National Academy of Sciences of the United States of America High 34244439
2014 Gas6-induced tissue factor expression in endothelial cells requires Axl receptor activation within caveolin-1-enriched lipid raft microdomains. Gas6 induces Axl and c-Src localization to these microdomains and activates Akt, ERK1/2, and c-Src. Axl, caveolin-1, or Akt siRNA knockdown blocks Gas6-induced tissue factor expression; c-Src inhibition blocks Akt but not ERK1/2 phosphorylation. siRNA knockdown (Axl, caveolin-1, c-Src, Akt), sucrose gradient fractionation of lipid rafts, Western blotting, confocal microscopy, tissue factor qPCR and immunofluorescence Journal of thrombosis and haemostasis : JTH High 24354620
2001 Gas6 induces beta-catenin stabilization (cytosolic pool) and TCF/Lef transcriptional activation in density-inhibited C57MG mammary cells via PI3K/S6K/Ras pathways. Gas6 activates Akt and inhibits GSK3 activity in a wortmannin-sensitive manner, preventing beta-catenin phosphorylation and degradation. Cell cycle analysis, PI3K/Akt/GSK3 phosphorylation assays, wortmannin inhibition, beta-catenin fractionation, TCF reporter assays in C57MG cells Molecular and cellular biology Medium 11154277
1999 The Axl ligand Gas6 protects Axl-expressing cells from serum deprivation-induced apoptosis and triggers greater mitogenic signaling when Axl is present, countering E1A-mediated growth suppression. E1A transcriptionally downregulates Axl expression, and forced re-expression of Axl with Gas6 restores survival and growth, placing Gas6/Axl downstream of E1A tumor-suppressive function. E1A expression cells with Axl re-expression, Gas6 treatment, apoptosis and proliferation assays, RT-PCR for Axl expression Molecular and cellular biology Medium 10567533
1998 Tyro3 receptor is expressed on mature osteoclasts and Gas6 directly induces Tyro3 phosphorylation in osteoclasts within 2-5 minutes. Gas6 and protein S directly enhance bone-resorbing activity of mature osteoclasts; this effect is blocked by the tyrosine kinase inhibitor herbimycin A. Gas6 does not affect osteoclast differentiation from bone marrow precursors. PCR cloning from primary osteoclasts, immunohistochemistry for Tyro3/TRAP, Tyro3 phosphorylation assay, bone resorption assays with herbimycin A inhibition Stem cells (Dayton, Ohio) Medium 9617898
2016 The Gas6-Axl interaction mediates endothelial cell uptake of platelet-derived microparticles (PMPs). TAM-blocking antibodies and siRNA knockdown of individual TAMs show that endothelial Axl specifically mediates PMP phagocytosis in a Gas6-dependent manner. Soluble Mer and Tyro3 do not form complexes with Gas6 in serum. Labeled PMP uptake assays, TAM-blocking antibodies, siRNA knockdown of Axl/Mer/Tyro3, flow cytometry, confocal/electron microscopy in human aortic and umbilical vein endothelial cells The Journal of biological chemistry Medium 27006397
2008 Glucose concentration alters Gas6-Axl signaling outputs in vascular smooth muscle cells: low glucose favors PI3K-p85/Akt/mTOR activation and anti-apoptotic effects, while high glucose favors Axl/SHP-2/ERK1/2 activation and enhanced migration. Co-immunoprecipitation shows glucose shifts Axl binding partners between p85-PI3K and SHP-2. Co-immunoprecipitation (Axl with p85-PI3K or SHP-2), Akt/mTOR/ERK phosphorylation immunoblots, apoptosis and migration assays under varying glucose concentrations Arteriosclerosis, thrombosis, and vascular biology Medium 18292389
2004 Gas6 activates Axl in human lens epithelial cells and mediates survival/anti-apoptotic responses via the AKT signaling pathway, protecting cells from serum starvation, TGF-β1, and TNF-α-induced apoptosis. Gas6 is present in bovine aqueous humor, and Axl is expressed and tyrosine-phosphorylated in normal lens tissue. Western blotting for Axl phosphorylation and AKT activation, cell viability, DNA condensation, caspase-3 activity assays in human lens epithelial cells Experimental eye research Medium 14667825
2013 Gas6 is mitogenic for schwannoma cells and increases schwannoma cell-matrix adhesion and survival by activating Axl. Gas6/Axl signaling recruits Src, focal adhesion kinase (FAK), and NFκB, which mediates Gas6/Axl-driven overexpression of survivin, cyclin D1, and FAK in schwannoma cells. Primary human schwannoma cell culture, Gas6 stimulation, Src/FAK/NFκB pathway inhibition, siRNA, survival and adhesion assays Oncogene Medium 23318455
2017 Gas6 promotes inflammatory (CCR2hiCX3CR1lo) monocyte recruitment during venous thrombosis. Gas6-/- mice show reduced recruitment of this monocyte subset. Gas6-dependent CCL2 expression in endothelial cells and CCR2 expression in monocytes regulate monocyte migration via JNK (c-Jun N-terminal kinase) signaling. Gas6 knockout mice, flow cytometry, clodronate monocyte depletion, anti-CCR2 and anti-CCL2 antibody depletion, JNK inhibition, in vitro migration assays, inferior vena cava deep venous thrombosis models Arteriosclerosis, thrombosis, and vascular biology High 28450294
2020 Phosphatidylethanolamine (PE) synergizes with phosphatidylserine (PS) to enhance GAS6-mediated PS recognition: liposomes containing both PE and PS bind GAS6 and are engulfed by AXL-expressing cells much more efficiently than PS-alone liposomes. PE on the same membrane surface maximizes PS receptor-mediated efferocytosis and virus entry. Liposome binding assays, GAS6-PS binding, AXL-expressing cell efferocytosis, pseudovirus infection inhibition assays Journal of virology Medium 33115868
2016 In the AXL decoy receptor study, engineering a high-affinity AXL decoy receptor (MYD1-72, ~93 femtomolar apparent affinity for GAS6) demonstrates that GAS6-AXL signaling abrogation leads to accumulation of DNA-damage markers (γH2AX, 53BP1, RAD51), revealing a role for AXL signaling in the cellular DNA damage response. Blockade of AXL signaling impairs homologous recombination. Engineered decoy receptor (MYD1-72), γH2AX/53BP1/RAD51 focus assays, in vitro and in vivo cancer models The Journal of clinical investigation Medium 27893463
2019 Gas6 regulates mitophagy during oocyte maturation: Gas6-silenced MII oocytes show decreased expression of mitophagy-related genes, increased MTOR activation, and mitochondrial accumulation/aggregation. Rapamycin treatment rescues mitophagy and restores mitophagy-related gene expression in Gas6-depleted oocytes, placing Gas6 upstream of MTOR in the mitophagy pathway. Gas6 siRNA silencing in oocytes, RNA-Seq, mitophagy gene expression by RT-PCR, MTOR/p-MTOR immunoblot, rapamycin rescue, Mdivi-1 treatment, mtDNA copy number measurement Scientific reports Medium 31316104
2018 Macrophage-derived Gas6 (from F4/80+CD11b+ macrophages in premalignant mammary lesions) activates Axl and downstream Akt and STAT3 signaling in premalignant cells, inducing altered E-cadherin expression and a malignant morphology. Deletion of stromal Gas6 delays early-stage mammary tumor progression and decreases tumor formation in vivo. 3D co-culture of macrophages and premalignant mammary cells, Gas6-/- stromal mice, Akt/STAT3 phosphorylation, E-cadherin immunostaining, in vivo tumor formation assays Oncogene Medium 30531835
2022 Neutrophils recruited to pancreatic cancer liver metastases after chemotherapy express Gas6, which activates AXL receptor on tumor cells to enable their regrowth. Recombinant Gas6 alone is sufficient to promote tumor cell proliferation ex vivo in patient-derived liver explants. Disruption of Gas6/AXL signaling combined with chemotherapy inhibits metastatic growth. Flow/mass cytometry, transcriptional analysis, mouse PDAC metastasis models, Gas6/AXL pathway inhibition, ex vivo patient-derived liver explants, recombinant Gas6 treatment Gut High 35022267
2024 GAS6 enriched in mesenchymal stem cell-derived extracellular vesicles promotes macrophage efferocytosis via MerTK/ERK/COX2 signaling pathway, reducing liver ischemia-reperfusion injury. GAS6 knockdown in EVs or MerTK inhibition (UNC2025) eliminates the protective efferocytosis-enhancing effects. Proteomic profiling of MSC-EVs, GAS6 lentiviral knockdown, MerTK inhibitor (UNC2025), efferocytosis assays, murine HIRI model, MerTK/ERK/COX2 phosphorylation immunoblot Cell death discovery Medium 39256347
2020 Gas6 promotes microglia efferocytosis of apoptotic neurons after subarachnoid hemorrhage (SAH) via Axl/Rac1 signaling. Recombinant Gas6 reduces neuroinflammation and brain injury in SAH mice; these effects are abolished by Axl or Rac1 inhibition/knockdown. Mouse SAH model, intraventricular rGas6 injection, Axl/Rac1 siRNA and inhibitors, efferocytosis in vivo and in vitro, neurological function tests, BBB integrity assays Translational stroke research Medium 36324028
2023 GAS6 overexpression (via AAV9) improves cardiac dysfunction in cecal ligation and puncture-induced sepsis by reducing NLRP3 inflammasome activation. GAS6 knockout elevates NLRP3 levels; GAS6 overexpression suppresses NLRP3 and downstream mitochondrial injury and apoptosis. This places NLRP3 as a downstream effector of GAS6/AXL signaling in cardiomyocytes. AAV9-mediated GAS6 overexpression and GAS6 KO mice, CLP sepsis model, NLRP3/mitochondrial injury/apoptosis assays, single-cell RNA sequencing Free radical biology & medicine Medium 37979891
2005 Gas6 and Axl are expressed by hepatic oval cells during liver regeneration and protect hepatocytic precursor (WB-F344) cells from apoptosis (but not by stimulating S-phase entry), acting via an autocrine/paracrine mechanism. Partial hepatectomy/acetylaminofluorene rat model, immunohistochemistry for Gas6/Axl, Gas6 treatment of WB-F344 cells, cell counts, flow cytometry, apoptosis assay Gastroenterology Medium 16285961
2024 Gas6/Axl activation inhibits ferroptosis during hepatic ischemia-reperfusion injury via the PI3K/AKT signaling pathway, reducing lipid peroxidation and iron accumulation. AXL inhibitor R428 exacerbates ferroptosis; PI3K inhibitor LY294002 blocks the anti-ferroptotic effect of Gas6/AXL activation. Mouse liver warm I/R model, hepatocyte hypoxia/reoxygenation model, recombinant Gas6 (AXL activator), R428 (AXL inhibitor), LY294002 (PI3K inhibitor), ferroptosis/lipid peroxidation assays Transplantation Medium 38725107
2016 Gas6 treatment of mouse optic nerve cultures increases oligodendrocyte numbers and myelin basic protein (MBP) expression, and activates STAT3 and Tyro3 receptor (by phosphorylation). In cerebellar slice cultures with lysolecithin-induced demyelination, co-treatment with Gas6 attenuates demyelination; Gas6 also downregulates MMP9. These effects are mediated through Tyro3. Mouse optic nerve and cerebellar slice cultures, MBP immunostaining, STAT3 and Tyro3 phosphorylation, Tyro3 knockdown/KO, MMP9 qPCR ASN neuro Medium 27630207
2020 Gas6 inhibits LPS-induced TNF-α upregulation and morphological activation in mouse microglia, acting through either Axl or Mer TAM receptors; the anti-inflammatory effect is present in both Axl-/- and Mer-/- microglia (indicating either receptor alone is sufficient). Axl-/- microglia have lower basal TNF-α expression. Primary microglia from WT, Mer-/-, Axl-/- mice, LPS stimulation, Gas6 pre-treatment, TNF-α RT-qPCR and ELISA, morphological analysis with ImageJ Frontiers in cellular neuroscience Medium 33192322
2020 In optic nerve and mixed glial cultures, Gas6 stimulates IL-10 and TGF-β expression, and this requires the presence of both Axl and Tyro3 (absent in either single KO). IL-10 mediates Gas6-induced MBP upregulation (neutralizing IL-10 antibody blocks it), linking Gas6 anti-inflammatory signaling to the pro-myelinating mechanism. Axl-/- and Tyro3-/- single KO glial cultures, Gas6 treatment, IL-10/TGF-β qPCR, anti-IL-10 neutralizing antibody, MBP immunostaining in optic nerve cultures Cells Medium 32722558
2023 PRAME is identified as a direct transcriptional target of Gas6/Axl/MAPK-ERK1/2 signaling in hepatocellular carcinoma. RNA-seq of Gas6-stimulated Axl-proficient vs. Axl-deficient HCC cells identifies PRAME as Gas6/Axl-regulated; Axl signaling inhibition or MEK/ERK inhibition reduces PRAME expression. PRAME augments cell migration and invasion and correlates with Axl-stratified patient outcomes. RNA-seq of matched Axl-expressing vs. Axl-deficient HCC cells, Axl inhibition, MAPK/ERK1/2 inhibition, PRAME gain/loss-of-function, proteomics, HCC patient tissue analysis Cancers Medium 37173882
2018 Protein S and Gas6 mediate efferocytosis of HIV-1-infected cells by bridging the Mer receptor tyrosine kinase on macrophages to phosphatidylserine exposed on the surface of infected cells. Phagocytosis assays with recombinant Gas6 and protein S, Mer-blocking antibodies, PS exposure measurement on HIV-1-infected cells Virology Medium 29304470

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis. Nature medicine 351 11175853
2006 Gas6 and protein S. Vitamin K-dependent ligands for the Axl receptor tyrosine kinase subfamily. The FEBS journal 295 17064312
2014 TAM receptors, Gas6, and protein S: roles in inflammation and hemostasis. Blood 277 24596417
2005 Structural basis for Gas6-Axl signalling. The EMBO journal 238 16362042
2005 Gas6 induces proliferation in prostate carcinoma cell lines expressing the Axl receptor. Journal of cellular physiology 174 15605394
2010 TNF-alpha, IL-6, and IL-1 expression is inhibited by GAS6 in monocytes/macrophages. Journal of leukocyte biology 163 20103767
2018 Targeting Gas6/TAM in cancer cells and tumor microenvironment. Molecular cancer 148 29386018
2021 Corticosterone inhibits GAS6 to govern hair follicle stem-cell quiescence. Nature 128 33790465
2009 Differential expression of Axl and Gas6 in renal cell carcinoma reflecting tumor advancement and survival. Clinical cancer research : an official journal of the American Association for Cancer Research 122 19567592
1997 GAS6 mediates adhesion of cells expressing the receptor tyrosine kinase Axl. The Journal of biological chemistry 118 9287338
2019 STAT6 induces expression of Gas6 in macrophages to clear apoptotic neutrophils and resolve inflammation. Proceedings of the National Academy of Sciences of the United States of America 116 31363052
2020 Gas6/Axl Signaling Pathway in the Tumor Immune Microenvironment. Cancers 114 32660000
2004 Vitamin K-dependent Gas6 activates ERK kinase and stimulates growth of cardiac fibroblasts. Biochemical and biophysical research communications 107 15184064
2013 GAS6 receptor status is associated with dormancy and bone metastatic tumor formation. PloS one 104 23637920
2017 Molecular insights of Gas6/TAM in cancer development and therapy. Cell death & disease 95 28333143
2016 Inhibition of the GAS6/AXL pathway augments the efficacy of chemotherapies. The Journal of clinical investigation 94 27893463
2005 Gas6 receptors Axl, Sky and Mer enhance platelet activation and regulate thrombotic responses. Journal of thrombosis and haemostasis : JTH 93 15733062
2001 Gas6 regulates mesangial cell proliferation through Axl in experimental glomerulonephritis. The American journal of pathology 90 11290560
2013 Gas6/Axl mediates tumor cell apoptosis, migration and invasion and predicts the clinical outcome of osteosarcoma patients. Biochemical and biophysical research communications 88 23684620
2010 Gas6 is complexed to the soluble tyrosine kinase receptor Axl in human blood. Journal of thrombosis and haemostasis : JTH 86 20088931
2022 Chemotherapy-induced infiltration of neutrophils promotes pancreatic cancer metastasis via Gas6/AXL signalling axis. Gut 83 35022267
2013 Axl/Gas6/NFκB signalling in schwannoma pathological proliferation, adhesion and survival. Oncogene 82 23318455
2008 Role of Gas6 in erythropoiesis and anemia in mice. The Journal of clinical investigation 82 18188450
2001 Gas6 induces mesangial cell proliferation via latent transcription factor STAT3. The Journal of biological chemistry 82 11546821
2008 Growth arrest-specific gene 6 (GAS6). An outline of its role in haemostasis and inflammation. Thrombosis and haemostasis 79 18841281
2021 The GAS6-AXL signaling pathway triggers actin remodeling that drives membrane ruffling, macropinocytosis, and cancer-cell invasion. Proceedings of the National Academy of Sciences of the United States of America 78 34244439
1999 The Gas6/Axl system: a novel regulator of vascular cell function. Trends in cardiovascular medicine 76 11094334
2012 Growth arrest-specific gene 6 (gas6) and vascular hemostasis. Advances in nutrition (Bethesda, Md.) 73 22516727
1998 Tyro 3 receptor tyrosine kinase and its ligand, Gas6, stimulate the function of osteoclasts. Stem cells (Dayton, Ohio) 71 9617898
2022 Anti-inflammatory clearance of amyloid-β by a chimeric Gas6 fusion protein. Nature medicine 69 35927581
2001 Gas6 induces growth, beta-catenin stabilization, and T-cell factor transcriptional activation in contact-inhibited C57 mammary cells. Molecular and cellular biology 67 11154277
2021 Therapeutic Targeting of the Gas6/Axl Signaling Pathway in Cancer. International journal of molecular sciences 64 34576116
2019 Gas6/TAM System: A Key Modulator of the Interplay between Inflammation and Fibrosis. International journal of molecular sciences 63 31614787
2010 GAS6 enhances repair following cuprizone-induced demyelination. PloS one 60 21203420
2008 Vitamin K-dependent actions of Gas6. Vitamins and hormones 60 18374195
2011 Gas6 deficiency prevents liver inflammation, steatohepatitis, and fibrosis in mice. American journal of physiology. Gastrointestinal and liver physiology 59 21350191
1999 Axl-gas6 interaction counteracts E1A-mediated cell growth suppression and proapoptotic activity. Molecular and cellular biology 56 10567533
2020 Pericyte FAK negatively regulates Gas6/Axl signalling to suppress tumour angiogenesis and tumour growth. Nature communications 54 32499572
2019 A Functional Role of GAS6/TAM in Nonalcoholic Steatohepatitis Progression Implicates AXL as Therapeutic Target. Cellular and molecular gastroenterology and hepatology 53 31689560
2018 LncRNA GAS6-AS2 promotes bladder cancer proliferation and metastasis via GAS6-AS2/miR-298/CDK9 axis. Journal of cellular and molecular medicine 48 30394665
2017 Small molecule inhibitors block Gas6-inducible TAM activation and tumorigenicity. Scientific reports 48 28272423
2004 Role of Gas6/Axl signaling in lens epithelial cell proliferation and survival. Experimental eye research 48 14667825
2013 GAS6 expression identifies high-risk adult AML patients: potential implications for therapy. Leukemia 47 24326683
2004 Human vitamin K-dependent GAS6: gene structure, allelic variation, and association with stroke. Human mutation 47 15108283
2020 Blockade of Stromal Gas6 Alters Cancer Cell Plasticity, Activates NK Cells, and Inhibits Pancreatic Cancer Metastasis. Frontiers in immunology 46 32174917
2016 The Gas6-Axl Protein Interaction Mediates Endothelial Uptake of Platelet Microparticles. The Journal of biological chemistry 46 27006397
2016 The Gas6/TAM System and Multiple Sclerosis. International journal of molecular sciences 46 27801848
2021 GAS6/AXL Inhibition Enhances Ovarian Cancer Sensitivity to Chemotherapy and PARP Inhibition through Increased DNA Damage and Enhanced Replication Stress. Molecular cancer research : MCR 45 34670865
2018 GAS6/TAM Pathway Signaling in Hemostasis and Thrombosis. Frontiers in medicine 44 29868590
2022 Gas6 Promotes Microglia Efferocytosis and Suppresses Inflammation Through Activating Axl/Rac1 Signaling in Subarachnoid Hemorrhage Mice. Translational stroke research 42 36324028
2020 Role of Vitamin K-Dependent Factors Protein S and GAS6 and TAM Receptors in SARS-CoV-2 Infection and COVID-19-Associated Immunothrombosis. Cells 40 32998369
2017 Gas6 Promotes Inflammatory (CCR2hiCX3CR1lo) Monocyte Recruitment in Venous Thrombosis. Arteriosclerosis, thrombosis, and vascular biology 39 28450294
2016 Gas6 Promotes Oligodendrogenesis and Myelination in the Adult Central Nervous System and After Lysolecithin-Induced Demyelination. ASN neuro 39 27630207
2009 Gas6 and the receptor tyrosine kinase Axl in clear cell renal cell carcinoma. PloS one 39 19888345
2008 Gas6-axl receptor signaling is regulated by glucose in vascular smooth muscle cells. Arteriosclerosis, thrombosis, and vascular biology 39 18292389
2004 Gas6, warfarin, and kidney diseases. Clinical and experimental nephrology 38 15619028
2020 Therapeutic aspects of the Axl/Gas6 molecular system. Drug discovery today 36 33002607
2023 Gas6/AXL pathway: immunological landscape and therapeutic potential. Frontiers in oncology 35 37265798
2021 Tumor perivascular cell-derived extracellular vesicles promote angiogenesis via the Gas6/Axl pathway. Cancer letters 34 34678434
2020 Phosphatidylethanolamine and Phosphatidylserine Synergize To Enhance GAS6/AXL-Mediated Virus Infection and Efferocytosis. Journal of virology 32 33115868
2018 Stromal Gas6 promotes the progression of premalignant mammary cells. Oncogene 32 30531835
2020 Gas6 Inhibits Toll-Like Receptor-Mediated Inflammatory Pathways in Mouse Microglia via Axl and Mer. Frontiers in cellular neuroscience 31 33192322
2024 Extracellular vesicles containing GAS6 protect the liver from ischemia-reperfusion injury by enhancing macrophage efferocytosis via MerTK-ERK-COX2 signaling. Cell death discovery 30 39256347
2020 Testosterone ameliorates vascular aging via the Gas6/Axl signaling pathway. Aging 30 32717722
2016 Endogenous GAS6 and Mer receptor signaling regulate prostate cancer stem cells in bone marrow. Oncotarget 30 27028863
2022 LncRNA GAS6-AS1 facilitates tumorigenesis and metastasis of colorectal cancer by regulating TRIM14 through miR-370-3p/miR-1296-5p and FUS. Journal of translational medicine 29 35962353
2020 The actin modulator hMENA regulates GAS6-AXL axis and pro-tumor cancer/stromal cell cooperation. EMBO reports 29 32909687
2020 Gas6 Induces Myelination through Anti-Inflammatory IL-10 and TGF-β Upregulation in White Matter and Glia. Cells 28 32722558
2006 Role of the growth arrest-specific gene 6 (gas6) product in thrombus stabilization. Blood cells, molecules & diseases 28 16564713
2019 Gas6/TAM Signaling Components as Novel Biomarkers of Liver Fibrosis. Disease markers 27 31583026
2017 Luteolin inhibits angiogenesis by blocking Gas6/Axl signaling pathway. International journal of oncology 26 28627676
1997 Sequence and functional relationships between androgen-binding protein/sex hormone-binding globulin and its homologs protein S, Gas6, laminin, and agrin. Steroids 26 9292933
2023 GAS6-based CAR-T cells exhibit potent antitumor activity against pancreatic cancer. Journal of hematology & oncology 25 37475048
2023 GAS6 attenuates sepsis-induced cardiac dysfunction through NLRP3 inflammasome-dependent mechanism. Free radical biology & medicine 25 37979891
2004 The role of the vitamin K-dependent growth factor Gas6 in glomerular pathophysiology. Current opinion in nephrology and hypertension 24 15199298
2019 Genetic loss of Gas6/Mer pathway attenuates silica-induced lung inflammation and fibrosis in mice. Toxicology letters 23 31284023
2019 Gas6/TAM Receptors in Systemic Lupus Erythematosus. Disease markers 22 31360267
2015 The Involvement of GAS6 Signaling in the Development of Obesity and Associated Inflammation. International journal of endocrinology 22 25954309
2005 Expression and role of Gas6 protein and of its receptor Axl in hepatic regeneration from oval cells in the rat. Gastroenterology 21 16285961
2016 Gas6 protein: its role in cardiovascular calcification. BMC nephrology 20 27230889
2019 Macrophage phenotypes and Gas6/Axl signaling in apical lesions. Journal of dental sciences 19 31528256
2023 Gas6/TAM Axis Involvement in Modulating Inflammation and Fibrosis in COVID-19 Patients. International journal of molecular sciences 18 36674471
2020 MRP8/14 mediates macrophage efferocytosis through RAGE and Gas6/MFG-E8, and induces polarization via TLR4-dependent pathway. Journal of cellular physiology 18 33128793
2019 Plasma sMer, sAxl and GAS6 levels correlate with disease activity and severity in lupus nephritis. European journal of clinical investigation 18 30588607
2018 Protein S and Gas6 induce efferocytosis of HIV-1-infected cells. Virology 18 29304470
2024 Gas6/AXL Alleviates Hepatic Ischemia/Reperfusion Injury by Inhibiting Ferroptosis via the PI3K/AKT Pathway. Transplantation 17 38725107
2022 Baseline Plasma Gas6 Protein Elevation Predicts Adverse Outcomes in Hospitalized COVID-19 Patients. Disease markers 17 35531477
2022 GAS6/Axl is associated with AMPK activation and attenuates H2O2-induced oxidative stress. Apoptosis : an international journal on programmed cell death 17 36580193
2020 USF1-mediated upregulation of lncRNA GAS6-AS2 facilitates osteosarcoma progression through miR-934/BCAT1 axis. Aging 17 32269179
2016 Exogenous Gas6 attenuates silica-induced inflammation on differentiated THP-1 macrophages. Environmental toxicology and pharmacology 17 27327525
2024 Administration of Gas6 attenuates lung fibrosis via inhibition of the epithelial-mesenchymal transition and fibroblast activation. Cell biology and toxicology 16 38578518
2024 Ozone promotes macrophage efferocytosis and alleviates neuropathic pain by activating the AMPK/Gas6-MerTK/SOCS3 signaling pathway. Frontiers in immunology 16 39628480
2019 Gas6 is a reciprocal regulator of mitophagy during mammalian oocyte maturation. Scientific reports 16 31316104
2023 PRAME Is a Novel Target of Tumor-Intrinsic Gas6/Axl Activation and Promotes Cancer Cell Invasion in Hepatocellular Carcinoma. Cancers 15 37173882
2023 Ozone alleviates MSU-induced acute gout pain via upregulating AMPK/GAS6/MerTK/SOCS3 signaling pathway. Journal of translational medicine 15 38066599
2022 Psoralidin protects against cerebral hypoxia/reoxygenation injury: Role of GAS6/Axl signaling. Phytotherapy research : PTR 15 35583809
2021 Gas6 Ameliorates Inflammatory Response and Apoptosis in Bleomycin-Induced Acute Lung Injury. Biomedicines 15 34829903
2020 Gas6 expression is reduced in advanced breast cancers. NPJ precision oncology 15 32352034
2017 Implication of a novel Gla-containing protein, Gas6 in the pathogenesis of insulin resistance, impaired glucose homeostasis, and inflammation: A review. Diabetes research and clinical practice 15 28453960
2014 Gas6-induced tissue factor expression in endothelial cells is mediated through caveolin-1-enriched microdomains. Journal of thrombosis and haemostasis : JTH 15 24354620

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