| 2000 |
Mutation/deletion of the Mertk gene (disrupting the splice acceptor site upstream of the second coding exon) in RCS rats causes failure of retinal pigment epithelial (RPE) cells to phagocytose shed photoreceptor outer segments, establishing MERTK as a receptor tyrosine kinase essential for this specialized phagocytic process. |
Positional cloning, genomic deletion mapping, transcript analysis, genetic concordance in RCS rat retinal dystrophy model |
Human molecular genetics |
High |
10699188
|
| 1994 |
MERTK (c-mer) encodes a novel 984-amino acid transmembrane receptor tyrosine kinase with extracellular immunoglobulin and fibronectin type III domains and the kinase signature KWIAIES, classified in the Axl family; it is expressed in peripheral blood monocytes and certain neoplastic lymphocyte lines but not in normal B- and T-lymphocytes. An alternatively spliced transcript encoding a truncated, potentially soluble receptor was also identified. |
Anti-phosphotyrosine antibody screening of cDNA expression library, sequence analysis, Northern blot RNA expression analysis |
Cell growth & differentiation |
High |
8086340
|
| 2004 |
MerTK activates phospholipase C gamma2 (PLCγ2) during macrophage phagocytosis of apoptotic thymocytes: exposure to apoptotic cells induces tyrosine phosphorylation of MerTK, association of PLCγ2 with MerTK, and phosphorylation of PLCγ2; PI-PLC inhibition blocks phagocytosis without impairing adhesion. |
Western blotting, immunoprecipitation (Co-IP), antibody cross-linking, pharmacological inhibition of PI-PLC (Et-18-OCH3, U73122) in peritoneal macrophages and J774 cells |
Journal of leukocyte biology |
High |
14704368
|
| 2004 |
Mer (MERTK) is the predominant Gas6 receptor expressed in mouse and human platelets (Axl and Rse not detected); Mer-deficient mice show decreased platelet aggregation in response to collagen, U46619, and PAR4 agonist, and are protected from collagen/epinephrine-induced pulmonary thromboembolism and ferric chloride-induced thrombosis in vivo, establishing a role for MERTK in platelet function and thrombosis. |
RT-PCR, Western blot, targeted gene disruption (Mer knockout mice), in vitro platelet aggregation assays, in vivo thrombosis models |
Arteriosclerosis, thrombosis, and vascular biology |
High |
15130911
|
| 2008 |
MerTK on dendritic cells (DCs) mediates apoptotic cell (AC)-induced inhibition of DC activation/maturation in a Gas6-dependent manner; DCs lacking MerTK kinase activity (NOD.MerTK(KD/KD)) are resistant to AC-induced suppression of proinflammatory cytokines and costimulatory molecule up-regulation, and mice lacking MerTK kinase activity show exacerbated autoimmune diabetes with increased activated pancreatic DCs. |
Kinase-dead knock-in mice, DC-T cell co-culture, cytokine secretion assays, adoptive transfer, streptozotocin-induced beta cell apoptosis model |
The Journal of experimental medicine |
High |
18195070
|
| 2010 |
Tubby and Tulp1 are novel MerTK ligands that act as bridging molecules for phagocytosis: tubby binds only MerTK while Tulp1 binds Tyro3, Axl, and MerTK; both ligands induce MerTK receptor phosphorylation and downstream signaling including non-muscle myosin II redistribution and co-localization with phagosomes; excess soluble MerTK extracellular domain blocks tubby/Tulp1-mediated phagocytosis; five minimal phagocytic determinants (K/R(X)(1-2)KKK) in Tulp1 N-terminus were defined as essential MerTK-binding motifs. |
Co-immunoprecipitation, receptor phosphorylation assays, blocking with soluble MerTK extracellular domain, phagocytosis assays, domain mapping by mutagenesis |
The EMBO journal |
High |
20978472
|
| 2012 |
MERTK overexpression in glioblastoma multiforme is associated with invasiveness; MERTK depletion disrupts rounded glioma cell morphology, decreases invasive capacity, and reduces expression and phosphorylation of myosin light chain 2, implicating actomyosin contractility as a downstream effector; MERTK also protects cells from DNA-damage-induced apoptosis in a kinase-activity-dependent manner. |
shRNA knockdown, overexpression of inactive MERTK mutant, invasion assays, Western blotting for myosin light chain 2 phosphorylation |
Oncogene |
Medium |
22469987
|
| 2013 |
In melanoma cells, GAS6 stimulation of MERTK activates MAPK/ERK, PI3K/AKT, and JAK/STAT downstream signaling pathways; shRNA-mediated MERTK inhibition reduces colony formation by up to 59% and diminishes tumor volume by 60% in xenograft models. |
GAS6 stimulation, Western blotting for downstream pathway phosphorylation, shRNA knockdown, soft agar colony formation, murine xenograft models |
The Journal of clinical investigation |
High |
23585477
|
| 2013 |
In AML cells, Gas6-stimulated MERTK activates prosurvival and proliferative signaling including phosphorylation of ERK1/2, p38, MSK1, CREB, ATF1, AKT, and STAT6; shRNA knockdown of MERTK increases myeloblast apoptosis 2-3-fold and decreases colony formation by 67-87%; MERTK knockdown prolongs survival in NOD-SCID-gamma xenograft mice. |
Gas6 ligand stimulation, Western blotting for signaling intermediates, shRNA knockdown, apoptosis assays, colony formation, murine xenograft model |
Oncogene |
High |
23474756
|
| 2013 |
In melanoma, shRNA-mediated MERTK knockdown reduces colony formation and cell migration in a CDC42-dependent manner and decreases cell survival in an AKT-dependent manner; a novel kinase-domain mutation MERTK(P802S) increases cell motility relative to wild-type MERTK. |
shRNA knockdown, colony formation assay, migration assay, small GTPase dependency experiments, site-directed mutagenesis |
Pigment cell & melanoma research |
Medium |
23617806
|
| 2014 |
MERTK overexpression in MCF10A epithelial cells stimulates efferocytosis in a gain-of-function capacity that is highly dependent on apoptotic cells (phosphatidylserine interface), also stimulates AKT-mediated chemoresistance, and promotes PD-L1 expression through apoptotic cell engagement; knockdown of MERTK in MDA-MB-231 breast cancer cells reduces efferocytosis. |
Stable MERTK overexpression, shRNA knockdown, efferocytosis assays, AKT pathway assays, PD-L1 expression analysis, soluble TAM receptor blocking |
The Journal of biological chemistry |
Medium |
25074939
|
| 2014 |
MERTK undergoes proteolytic cleavage to release a soluble sMerTK form from RPE cells; sMerTK acts as a decoy receptor blocking MerTK ligands and thereby limiting phagocytic outer segment binding; blocking MERTK cleavage increases POS binding; MFG-E8 (integrin ligand) markedly increases both phagocytosis and sMerTK shedding. |
Conditioned media analysis, RPE-J cell phagocytosis assays, metalloprotease inhibitors, MERTK cleavage blocking reagents, interphotoreceptor matrix analysis |
The Journal of biological chemistry |
Medium |
25538233
|
| 2015 |
Mer receptor mediates both tethering and phagocytosis of apoptotic cells by macrophages; Mer-mediated tethering and subsequent AC engulfment can be distinguished by their differential requirement for Mer kinase activity (tethering is kinase-independent, engulfment is kinase-dependent); Protein S and Gas6 show extremely rapid binding kinetics to phosphatidylserine-displaying apoptotic cells; Mer-mediated phagocytosis can occur independently of αV integrins. |
Kinase-dead Mer mutants, phagocytosis assays, tethering assays, ligand binding kinetics, integrin-blocking experiments |
Cell death & disease |
High |
25695599
|
| 2015 |
MERTK expressed on tolerogenic DCs suppresses T cell activation through competition for PROS1 (Protein S): DC-expressed MERTK acts as a decoy to neutralize PROS1, which otherwise drives an autocrine pro-proliferative MERTK-PROS1 signaling loop in TCR-activated T cells; Mer-Fc protein mimicking DC MERTK suppresses naïve and memory T cell activation. |
Neutralization of MERTK in allogeneic MLR, Mer-Fc soluble receptor competition assay, DC-T cell co-cultures, PROS1 blocking |
Journal of leukocyte biology |
Medium |
25624460
|
| 2015 |
Tyro3 gene dosage genetically modifies Mertk-associated retinal degeneration: loss of Tyro3 function accelerates photoreceptor degeneration in Mertk knockout mice; TYRO3 protein co-localizes with nascent photoreceptor outer segment phagosomes in primary RPE cells; Tyro3 expression in RPE is controlled by a cis-acting eQTL with the B6 allele conferring ~3-fold higher expression. |
Genetic mapping, Mertk/Tyro3 double-knockout mouse models, immunolocalization, primary RPE phagocytosis assay, Tyro3 overexpression in cultured cells |
PLoS genetics |
High |
26656104
|
| 2016 |
MERTK knockdown in prostate cancer cells (but not AXL or TYRO3 knockdown) induces a decreased P-ERK1/2:P-p38 ratio, increased p27, NR2F1, SOX2, and NANOG expression, elevated H3K9me3 and H3K27me3, and G1/G0 arrest—features of cellular dormancy; this is reversed by p38 inhibitor SB203580, implicating MAP kinases in MERTK-dependent dormancy escape. |
shRNA and siRNA knockdown, cell cycle analysis, Western blotting for kinase phosphorylation, histone methylation analysis, intra-cardiac injection xenograft model, pharmacological p38 inhibition |
Journal of cellular biochemistry |
Medium |
27753136
|
| 2017 |
MERTK cleavage in atherosclerotic lesion macrophages reduces efferocytosis and promotes plaque necrosis and impaired resolution; myeloid-specific expression of a cleavage-resistant MerTK variant in Ldlr-/- mice results in higher macrophage MerTK, lower soluble Mer, improved efferocytosis, smaller necrotic cores, thicker fibrous caps, and increased proresolving lipid mediators. |
Cleavage-resistant MerTK knock-in mice (myeloid-specific), atherosclerosis model (fat-fed Ldlr-/- mice), efferocytosis assays, lesion histology, lipid mediator analysis; human carotid plaque correlation |
The Journal of clinical investigation |
High |
28067670
|
| 2017 |
MerTK crystal structure determined in complex with a macrocyclic pyrimidine inhibitor (UNC2541), showing that macrocycles bind in the ATP-binding pocket of MerTK; structure-based drug design exploiting this binding site yields sub-micromolar inhibitors with MerTK selectivity. |
X-ray crystallography of MerTK–inhibitor co-crystal, structure-activity relationship studies, cell-based phospho-ELISA |
ChemMedChem |
High |
28032464
|
| 2017 |
X-ray co-crystal structure of MerTK complexed with macrocyclic pyrrolopyrimidine inhibitor (UNC3133) shows macrocycles binding in the ATP-binding pocket; cell-based MerTK phosphorylation ELISA confirms sub-40 nM activity. |
X-ray crystallography, cell-based MerTK phospho-protein ELISA, structure-activity relationship studies |
ACS medicinal chemistry letters |
High |
27994735
|
| 2017 |
Positive selection in MERTK's signal peptide (G14C mutation) decreases MERTK expression without affecting trafficking or half-life; amino acid substitutions and insertions in the human transmembrane domain create a new self-clustering interaction motif that enhances MERTK avidity, counteracting reduced expression; lower MERTK expression reduces Ebola virus-like particle binding, consistent with antagonistic coevolution against viral hijacking. |
Ancestral sequence reconstruction, site-directed mutagenesis, expression analysis, MERTK trafficking/half-life assays, virus-like particle binding assay |
Molecular biology and evolution |
Medium |
28369510
|
| 2018 |
MERTK inhibition (genetic deletion or MRX-2843 small-molecule inhibitor) in the leukemia microenvironment decreases PD-L1 and PD-L2 expression on CD11b+ monocytes/macrophages, indirectly decreases PD-1 on CD4+ and CD8+ T cells, reduces FOXP3+ Tregs, and increases T cell activation, demonstrating that MERTK controls the PD-1 immunosuppressive axis. |
Mertk-/- mice, MRX-2843 small-molecule inhibitor, xenograft and syngeneic leukemia mouse models, flow cytometry for immune cell populations and checkpoint marker expression |
JCI insight |
High |
30385715
|
| 2018 |
MERTK upregulation mediates intrinsic and adaptive resistance to AXL-targeting agents in HNSCC, TNBC, and NSCLC; ectopic overexpression of MERTK in AXL-inhibitor-sensitive models confers resistance; dual inhibition of AXL and MERTK produces synergistic blockade of downstream signaling and reduced tumor growth in vivo. |
AXL inhibitor treatment, siRNA knockdown, MERTK overexpression in sensitive cell lines, patient-derived xenografts, downstream signaling Western blotting, tumor growth in vivo |
Molecular cancer therapeutics |
Medium |
30093568
|
| 2019 |
MERTK on activated human CD8+ T cells acts as a late costimulatory receptor: TCR-activated CD8+ T cells express MERTK and the ligand PROS1 from day 2 post-activation; PROS1-mediated MERTK signaling increases proliferation and secretion of effector/memory cytokines; MERTK signaling influences memory CD8+ T cell differentiation; knockdown/inhibition confirmed the costimulatory effect is MERTK-dependent. |
Flow cytometry for MERTK/PROS1 expression, MERTK knockdown, pharmacological inhibition, transcriptomic and metabolic analysis, TIL expansion assays with autologous tumor killing |
Cancer immunology research |
Medium |
31266785
|
| 2019 |
Macrophage MerTK promotes liver fibrosis in NASH via an ERK-TGFβ1 pathway that activates hepatic stellate cells; ADAM17-mediated MerTK cleavage decreases during steatosis-to-NASH transition; mice with a cleavage-resistant MerTK mutant have increased NASH fibrosis; holo- or myeloid-specific Mertk knockout decreases NASH fibrosis. |
Mertk knockout mice (holo and myeloid-specific), cleavage-resistant MerTK knock-in, NASH diet models, ERK-TGFβ1 pathway analysis, hepatic stellate cell activation assays |
Cell metabolism |
High |
31839486
|
| 2019 |
CDCev-derived extracellular vesicles induce sustained MerTK expression in macrophages through transfer of microRNA-26a (which suppresses Adam17, thereby reducing MerTK cleavage), enhancing efferocytosis; cardioprotection by this mechanism is lost in MerTK-deficient animals. |
In vitro efferocytosis assays with bone marrow-derived macrophages, microRNA-26a transfer analysis, Adam17 expression, transgenic MerTK-deficient rodent models, single-cell RNA sequencing |
Arteriosclerosis, thrombosis, and vascular biology |
Medium |
31434491
|
| 2020 |
During acute viral infection with VSV, Mertk is activated by apoptotic cells and induces IL-10 and TGF-β production; Mertk-/- mice lack this induction and do not develop innate anergy; mechanistically, Mertk signaling upregulates SOCS1 and SOCS3 to suppress innate immune responses; dexamethasone enhances innate anergy in a Mertk-dependent manner. |
Mertk-/- mice, VSV infection model, cytokine measurements (IL-10, TGF-β), SOCS1/SOCS3 expression analysis, dexamethasone treatment |
Cell reports |
Medium |
32187540
|
| 2020 |
Tim-4 collaborates with Mertk during efferocytosis through a physical interaction between the IgV domain of Tim-4 and the fibronectin type-III domain of Mertk; disruption of this interaction with soluble GST-MertkFnIII abolishes the enhancement of efferocytosis by Mertk in Tim-4-mediated phagocytosis. |
Co-immunoprecipitation, immunofluorescence, proximity ligation assay, domain-specific blocking with GST-MertkFnIII, efferocytosis assays |
Cells |
Medium |
32640697
|
| 2021 |
Mertk kinase activity is essential for efferocytosis: a newly developed kinase-dead Mertk mouse model demonstrates that MERTK kinase activity is required for peritoneal macrophage efferocytosis in vivo; this is conserved in human iPSC-derived macrophages where MERTK blocking antibodies and small molecule inhibitors reduce GAS6-enhanced efferocytosis. |
Kinase-dead Mertk knock-in mice, peritoneal efferocytosis assay in vivo, human iPSC-derived macrophages, blocking antibodies, small molecule inhibitors, GAS6 agonism |
Cell death & disease |
High |
34035216
|
| 2021 |
Microglial MERTK mediates phosphatidylserine-dependent elimination of inhibitory post-synapses: conditional Cdc50a deletion in neurons induces phosphatidylserine exposure on somas and selective loss of inhibitory post-synapses; ablation of microglia or deletion of microglial Mertk prevents inhibitory post-synapse loss and seizures, establishing MERTK as the microglial phagocytic receptor that recognizes phosphatidylserine on inhibitory post-synapses. |
Neuron-specific Cdc50a conditional knockout, microglial ablation, microglial Mertk conditional knockout, synaptic marker quantification, EEG seizure monitoring |
The EMBO journal |
High |
34013588
|
| 2021 |
Mertk is required for efficient microglial clearance of myelin debris and subsequent remyelination: Mertk-KO mice show impaired myelin debris clearance and remyelination following demyelination; Mertk-KO brains show attenuated overall microglial response to demyelination but elevated proportion of IFN-responsive microglia; IFNγ further impedes microglial myelin clearance and inhibits oligodendrocyte differentiation downstream of Mertk deficiency. |
Mertk knockout mice, cuprizone demyelination model, single-cell RNA sequencing, myelin debris clearance quantification, remyelination histology |
Cell reports |
High |
33691116
|
| 2021 |
ODC-dependent putrescine synthesis maintains basal MerTK expression via a histone methylation-dependent transcriptional mechanism; reduced MerTK in ODC-deficient macrophages impairs MerTK-ERK1/2-dependent IL-10 production upon apoptotic cell exposure; putrescine treatment of ODC-deficient macrophages restores MerTK expression and AC-induced IL-10. |
ODC-deficient macrophages, RNA sequencing, ChIP or histone methylation assays, MerTK expression/signaling analysis, zymosan peritonitis model, nanoparticle-mediated ODC silencing in atherosclerosis regression model |
Arteriosclerosis, thrombosis, and vascular biology |
Medium |
33406854
|
| 2021 |
MERTK on mononuclear phagocytes in pancreatic islets promotes T cell regulation by reducing the sensitivity of T cell scanning for cognate antigen, leading to reduced T cell activation and effector function at disease sites; MERTK also regulates T cell arrest in melanoma tumors; loss of mononuclear phagocyte MERTK activity accelerates T cell-mediated islet destruction. |
Mertk-/- mice, two-photon intravital imaging of T cell behavior in islets and tumors, type 1 diabetes models, tumor models |
The Journal of experimental medicine |
Medium |
34415994
|
| 2022 |
MERTK interaction with ligand PROS1 in osteoblasts negatively regulates osteoblast differentiation via the VAV2-RHOA-ROCK axis, increasing cell contractility and motility; osteoblast-targeted MERTK deletion increases bone mass; TYRO3 antagonizes this MERTK effect in osteoblasts; pharmacological MERTK blockade (R992) increases osteoblast numbers and bone formation in mice. |
Osteoblast-specific Mertk and Tyro3 conditional knockout mice, PROS1 ligand stimulation, VAV2/RHOA/ROCK pathway analysis, pharmacological MERTK inhibitor (R992), bone histomorphometry, cancer bone metastasis models |
Nature communications |
High |
36509738
|
| 2022 |
N-glycosylation of MERTK at asparagine 294 and 454 stabilizes the receptor and promotes oncogenic transformation in hepatocellular carcinoma; non-glycosylated MERTK localizes to the nucleus and is required for HCC cell survival under stress; MERTK ablation increases ROS production and promotes switching from glycolytic to oxidative phosphorylation metabolism. |
N-glycosylation site mutagenesis, subcellular fractionation, metabolic assays (glycolysis/OXPHOS), ROS measurement, tumor growth assays |
Redox biology |
Medium |
35728303
|
| 2022 |
MerTK activation by Gas6 induces MERTK phosphorylation and downstream Akt activation in macrophages; MerTK-activated macrophages produce a secretome (including VEGF-A) that promotes HSC migration, proliferation, viability, and profibrogenic factor expression through STAT3 and p38 signaling in hepatic stellate cells; these effects are specifically blocked by MerTK pharmacologic inhibition (UNC569) or knockdown. |
Gas6 stimulation, UNC569 pharmacological inhibition, siRNA knockdown, conditioned medium transfer to HSCs, Boyden chamber migration, BrdU proliferation, STAT3/p38/ERK1/2 Western blotting |
JHEP reports |
Medium |
35252828
|
| 2022 |
Arid3a negatively regulates Mertk transcription in macrophages by directly binding to the Mertk promoter (confirmed by ChIP-seq and luciferase reporter assay); Arid3a-deficient macrophages show enhanced Mertk-mediated efferocytosis of apoptotic cholangiocytes; myeloid-specific Arid3a deletion alleviates cholestatic liver injury in a Mertk-dependent manner. |
ChIP-seq, luciferase reporter assay, myeloid-specific Arid3a knockout mice, three cholestatic mouse models, Mertk inhibitor (UNC2025) in vivo and in vitro, flow cytometry |
Journal of hepatology |
High |
37659731
|
| 2022 |
MERTK expressed in endothelial cells maintains endothelial barrier function by regulating adherens junction structure, junction protein levels, and basal Rac1 activity; siRNA knockdown of MERTK in human pulmonary microvascular endothelial cells enhances neutrophil transendothelial migration and increases dextran permeability. However, endothelial cell-specific Mertk deletion in vivo (iEC Mertk-/- mice) did not replicate aggravated inflammation in P. aeruginosa pneumonia. |
siRNA knockdown in primary human endothelial cells, dextran permeability assay, Rac1 activity assay, adherens junction analysis, inducible endothelial-specific Mertk-/- mice, in vivo P. aeruginosa pneumonia model |
PloS one |
Medium |
31805065
|
| 2023 |
Stress hormones increase MERTK expression in astrocytes through glucocorticoid receptor (GR) activation, driving astrocyte-mediated excitatory post-synapse phagocytosis; early social deprivation activates the GR-MERTK pathway specifically in astrocytes; ablation of GR or MERTK in astrocytes prevents loss of excitatory synapses, abnormal neuronal network activity, and behavioral abnormalities. |
Astrocyte-specific conditional knockout of GR and Mertk, in vitro stress hormone treatment, human brain organoid experiments, synapse quantification, EEG, behavioral assays |
Immunity |
High |
37527657
|
| 2023 |
KLF4 transcription factor mediates training-induced MERTK upregulation in alveolar macrophages; KLF4-driven MERTK expression expands a MERTKhiMarcohiCD163+F4/80low tissue-resident AM subset with enhanced efferocytosis capacity; adoptive transfer of trained AMs restricts inflammatory lung injury. |
Transcriptomic analysis, KLF4 ChIP (implied by KLF4 overexpression/knockdown), single-cell mass cytometry, lineage tracing, adoptive transfer experiments |
The Journal of experimental medicine |
Medium |
37615937
|
| 2023 |
EphA4 receptor tyrosine kinase suppresses MERTK expression and efferocytosis in monocytes/macrophages via inhibition of the ERK/Stat6 signaling pathway; loss of EphA4 increases mRNA expression of Mertk and Gas6, enhances efferocytosis, and improves functional outcome after brain injury; selective ERK and Stat6 inhibitors attenuate this effect. |
GFP bone marrow chimeric EphA4 knockout mice, single-cell RNAseq, in vitro efferocytosis assay, ERK/Stat6 inhibitors, immunolocalization of p-ERK/p-Stat6 with MERTK |
Journal of neuroinflammation |
Medium |
37941008
|
| 2024 |
MerTK renders hepatocellular carcinoma resistant to anti-PD-1/PD-L1 therapy by limiting ferroptosis via upregulation of SLC7A11 through the ERK/SP1 pathway, and by facilitating MDSC recruitment to the tumor microenvironment; MerTK inhibition (sitravatinib) sensitizes resistant HCC to anti-PD-L1 by promoting ferroptosis and decreasing MDSC infiltration. |
Syngeneic mouse HCC models, MERTK knockdown/overexpression, SLC7A11 expression analysis, ERK/SP1 pathway analysis, MDSC flow cytometry, sitravatinib pharmacological treatment |
Cell reports. Medicine |
Medium |
38382467
|
| 2024 |
MERTK is identified as a TGFβ-inducible effector of fibrosis in multiple organs; MERTK induces TGFβ expression and drives TGFβ signaling in a positive feedback loop; MERTK regulates both canonical and noncanonical TGFβ signaling; MERTK increases transcription of fibrosis genes by modulating chromatin accessibility and RNA polymerase II activity; pharmacological MERTK inhibition reduces fibrosis in liver, kidney, and lung mouse models even after fibrosis is established. |
Human HSC and macrophage in vitro studies, three mouse fibrosis models (liver, kidney, lung), chromatin accessibility assays, RNA polymerase II activity assays, TGFβ signaling analysis, pharmacological MERTK inhibition |
Science translational medicine |
High |
38569018
|
| 2024 |
MerTK mediates non-inflammatory phagocytosis of alpha-synuclein fibrils by human microglia: pharmacological MerTK inhibition and siRNA knockdown both decrease the rate of alpha-synuclein fibril internalization; alpha-synuclein fibril uptake via MerTK does not induce pro-inflammatory cytokines (IL-6, TNF) and downmodulates IL-1β, consistent with non-inflammatory MerTK-mediated phagocytosis. |
Human primary and iPSC-derived microglia, pharmacological MerTK inhibition, siRNA knockdown, cytokine secretion assays, fibril internalization quantification |
Brain |
Medium |
37671615
|
| 2024 |
ALKAL1, a target gene of the aryl hydrocarbon receptor (AhR), facilitates MerTK phosphorylation in tumor-associated macrophages, resulting in heightened phagocytic activity and subsequent polarization toward an immunosuppressive phenotype; AhR antagonist delivery to tumor-associated macrophages suppresses MerTK expression and improves anti-PD-L1 efficacy. |
Single-cell RNAseq, adoptive transfer of MerTK+ macrophages, mechanistic ALKAL1/AhR studies, AhR antagonist in mannosylated micelles, MerTK phosphorylation assays |
Science advances |
Medium |
39365866
|
| 2025 |
Staphylococcus aureus vesicles (SAVs) activate the TLR2-MyD88-p38 MAPK signaling pathway to promote cleavage/shedding of MerTK from macrophage surfaces, thereby inhibiting efferocytosis; selective p38 MAPK inhibition prevents MerTK shedding, restores efferocytosis, and accelerates wound healing. |
Purified SAVs, TLR2/MyD88/p38 pathway analysis (Western blot, siRNA), MerTK shedding quantification by flow cytometry and RNA-seq, p38 MAPK inhibitor treatment, in vivo wound healing model |
Cell communication and signaling |
Medium |
39780180
|
| 2013 |
UNC1062 is a pyrazolopyrimidine sulfonamide MerTK inhibitor with IC50 = 1.1 nM; in cancer cells it inhibits MerTK phosphorylation and colony formation in soft agar, confirming the functional importance of MerTK kinase activity in oncogenic transformation. |
Kinase biochemical assay, cell-based MerTK phosphorylation assay, soft agar colony formation |
European journal of medicinal chemistry |
Medium |
23693152
|
| 2022 |
BMS794833 inhibits MERTK by binding to both the ATP-binding pocket and an allosteric back pocket (rendering MERTK inactive), as shown by X-ray co-crystal structure; it competitively inhibits MERTK autophosphorylation in macrophages and significantly inhibits macrophage efferocytosis in vitro and in vivo. |
X-ray co-crystal structure of BMS794833-MERTK, homogeneous time-resolved fluorescence kinetic assay, Western blotting for MERTK autophosphorylation, real-time efferocytosis monitoring, in vivo mouse efferocytosis model |
Experimental & molecular medicine |
High |
36056187
|
| 2009 |
MerTK promotes macrophage survival following oxidative stress (H2O2): H2O2 triggers Mer phosphorylation in a Gas6-dependent manner; MerTK signaling increases pAkt and pErk1/2 (3-fold and 4.5-fold respectively), decreases PARP and Caspase-3 cleavage, and provides up to 2-fold enhanced survival to macrophages; warfarin or MerFc (blocking Gas6) prevents H2O2-mediated Mer activation. |
H2O2 treatment, warfarin/MerFc Gas6 inhibition, Mer knockout macrophages, Western blotting for pAkt/pErk/PARP/Caspase-3, cell viability assay |
Journal of leukocyte biology |
Medium |
19386698
|
| 2009 |
MerTK in dendritic cells negatively regulates BAFF production: mertk-/- mice contain elevated splenic DCs with elevated proportion of BAFF-secreting cells; mertk-/- BMDCs also have elevated BAFF-secreting cells at rest and after LPS or apoptotic cell stimulation; however, despite more BAFF-secreting cells, mertk-/- BMDCs are not superior at promoting B cell survival. |
mertk-/- mice, flow cytometry, BAFF decoy receptor blocking, DC-B cell co-culture survival assay |
Autoimmunity |
Medium |
19301199
|
| 2022 |
Pentoxifylline (PTX) alleviates ischemic white matter injury through PPAR-γ nuclear translocation, which upregulates Mertk expression in microglia; microglia-specific Mertk knockout blocks the therapeutic effects of PTX in BCAS model; PTX-upregulated Mertk enhances microglial phagocytosis of myelin debris. |
BCAS mouse model (bilateral common carotid artery stenosis), microglia-specific Mertk knockout mice, Mertk inhibitor, PPAR-γ inhibitor, immunofluorescence, Western blotting, flow cytometry |
Journal of neuroinflammation |
Medium |
35642056
|