Affinage

CSF1R

Macrophage colony-stimulating factor 1 receptor · UniProt P07333

Length
972 aa
Mass
108.0 kDa
Annotated
2026-04-28
100 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CSF1R (c-Fms) is a receptor tyrosine kinase that serves as the primary signaling receptor for CSF-1 (M-CSF) and IL-34, governing the proliferation, differentiation, survival, and functional activation of mononuclear phagocytes, osteoclasts, microglia, and certain neurons. Upon ligand binding, autoinhibition mediated by the juxtamembrane domain—which wedges against the kinase active site to prevent activation loop remodeling—is released, enabling autophosphorylation and recruitment of downstream effectors including DAP12/Syk (for osteoclast cytoskeletal reorganization), PI3K/Akt, and ERK, while adaptors Lnk and STAP-2 attenuate signaling by suppressing receptor phosphorylation (PMID:2408759, PMID:17292918, PMID:18691974, PMID:20571037). CSF1R expression is controlled by a combination of posttranscriptional regulation—through competing mRNA-binding proteins HuR (stabilizing) and vigilin (destabilizing)—and epigenetic mechanisms including Pax5-mediated transcriptional silencing in B cells and a FIRE super-enhancer whose deletion selectively ablates tissue-resident macrophage populations while sparing monocytes (PMID:20974809, PMID:16482219, PMID:31324781). Loss-of-function mutations in the CSF1R kinase domain cause hereditary diffuse leukoencephalopathy with spheroids (HDLS) through defective autophosphorylation and impaired autophagy, whereas C-terminal Tyr969-to-Phe mutations that abolish negative regulatory phosphorylation confer oncogenic potential (PMID:31827782, PMID:3027579).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1985 High

    The identity of the CSF-1 receptor was unknown; demonstrating that the c-fms proto-oncogene product is a transmembrane glycoprotein with intrinsic tyrosine kinase activity that specifically binds CSF-1 established the molecular basis of macrophage growth factor signaling.

    Evidence Immunoprecipitation with anti-v-fms antisera, CSF-1 binding assay, and immune complex kinase assay in membrane preparations

    PMID:2408759

    Open questions at the time
    • Ligand-induced receptor conformational changes not resolved
    • Downstream signaling pathways not yet mapped
    • Second ligand IL-34 not yet identified
  2. 1987 High

    How oncogenic v-fms differs from c-fms was unclear; showing that Tyr969 phosphorylation negatively regulates the receptor and that its mutation to Phe (as in v-fms) is required for transformation established a C-terminal autoinhibitory mechanism and the molecular basis of c-fms oncogenic activation.

    Evidence Site-directed mutagenesis of Tyr969→Phe969, NIH 3T3 transformation assays with chimeric v-fms/c-fms constructs co-transfected with CSF-1 cDNA

    PMID:3027579

    Open questions at the time
    • Signaling partners recruited to phospho-Tyr969 not identified
    • Whether Tyr969 mutation alone is sufficient for in vivo tumorigenesis unknown
  3. 1989 High

    Whether c-fms expression is controlled transcriptionally or posttranscriptionally was uncertain; nuclear run-on and mRNA half-life experiments demonstrated that a labile protein stabilizes c-fms mRNA, establishing posttranscriptional regulation as a major control mechanism.

    Evidence Nuclear run-on transcription assays, mRNA half-life measurement with cycloheximide in differentiating HL-60 cells and monocytes

    PMID:2523515

    Open questions at the time
    • Identity of the stabilizing protein not determined at this time
    • Cis-element in c-fms mRNA mediating stability not mapped
  4. 1990 High

    Whether CSF-1R kinase activity alone suffices for mitogenic signaling was untested; a chimeric receptor study proved that activation of the intracellular kinase domain without CSF-1 binding is sufficient to drive autophosphorylation, receptor downmodulation, and mitogenesis.

    Evidence Chimeric CD2-ectodomain/CSF-1R-kinase receptor in NIH 3T3 cells stimulated with anti-CD2 antibody

    PMID:1691441

    Open questions at the time
    • Which specific tyrosine autophosphorylation sites mediate mitogenic signaling not mapped
    • Downstream signaling intermediates not identified
  5. 2003 High

    How the AML1-ETO fusion oncoprotein deregulates c-FMS in t(8;21) leukemia was unknown; ChIP and in vivo footprinting showed AML1-ETO binds extended intronic regulatory sequences and remodels histone marks, establishing an epigenetic mechanism for c-FMS dysregulation in leukemia.

    Evidence In vivo footprinting and chromatin immunoprecipitation with histone modification analysis in normal versus t(8;21) leukemic cells

    PMID:12773394

    Open questions at the time
    • Whether AML1-ETO binding directly alters c-FMS transcription output not quantified
    • Functional consequence for macrophage differentiation not tested
  6. 2004 High

    How c-fms is silenced during B-cell commitment and how extrinsic signals regulate its expression in macrophages were unresolved; two studies showed that Pax5 represses c-fms by displacing RNA polymerase II from the locus (reversible upon Pax5 deletion), and that gp130-ERK1/2 signaling positively regulates c-fms expression and M-CSF responsiveness in macrophages.

    Evidence Conditional Pax5 deletion with ChIP and DNase I hypersensitivity in B cells; gp130 signaling mutant knock-in macrophages with pharmacological ERK1/2 inhibition

    PMID:14749363 PMID:15483629

    Open questions at the time
    • Direct Pax5 DNA-binding site relative to c-fms promoter not fully mapped at this point
    • Whether ERK1/2 acts on c-fms transcription or mRNA stability not distinguished
  7. 2006 High

    The mechanism by which Pax5 silences c-fms was incompletely understood; detailed ChIP showed Pax5 is recruited to the c-fms transcription start sites, directly displacing the basal transcription machinery and sequentially shutting down all cis-regulatory elements.

    Evidence Chromatin immunoprecipitation and DNase I hypersensitivity with conditional Pax5 expression system

    PMID:16482219

    Open questions at the time
    • Whether Pax5-mediated silencing involves DNA methylation changes not fully resolved
    • Kinetics of reactivation upon Pax5 removal in vivo not measured
  8. 2007 High

    The structural basis of CSF1R autoinhibition was unknown; the 2.7 Å crystal structure revealed that juxtamembrane domain tyrosines wedge into a hydrophobic pocket adjacent to the ATP-binding site, locking the activation loop in an inactive conformation—a mechanism shared with c-Kit and Flt3.

    Evidence X-ray crystallography of the cytosolic kinase plus juxtamembrane domain at 2.7 Å resolution

    PMID:17292918

    Open questions at the time
    • Full-length extracellular–transmembrane–kinase structure not available
    • Dynamics of JM release upon ligand binding not captured
  9. 2008 High

    How CSF-1R signals to the osteoclast cytoskeleton was unclear; demonstrating that c-Fms Tyr559 nucleates a DAP12/Syk signaling complex essential for cytoskeletal reorganization established a non-canonical ITAM-based pathway downstream of CSF-1R in osteoclasts.

    Evidence Co-immunoprecipitation, retroviral reconstitution of DAP12/Syk-null osteoclast precursors with wild-type and mutant constructs, cytoskeletal analysis

    PMID:18691974

    Open questions at the time
    • Whether DAP12/Syk pathway operates in macrophages outside osteoclasts not tested
    • Direct substrates of Syk downstream of c-Fms not identified
  10. 2010 High

    Negative regulators that restrain CSF-1R signaling magnitude were largely unknown; identification of Lnk and STAP-2 as adaptors that constitutively bind c-Fms and suppress M-CSF-induced phosphorylation, Akt activation, and macrophage migration established feedback attenuation mechanisms.

    Evidence Co-immunoprecipitation, Lnk knockout macrophages, STAP-2 overexpression, Akt/ERK phosphorylation kinetics, migration assays

    PMID:17512498 PMID:20571037

    Open questions at the time
    • Whether Lnk and STAP-2 compete for the same binding site on c-Fms not determined
    • In vivo macrophage phenotypes of STAP-2 loss not tested
  11. 2010 High

    The posttranscriptional regulators of c-fms mRNA identified in 1989 were molecularly uncharacterized; demonstrating that vigilin and HuR compete for a 69-nt element in the c-fms 3′ UTR with opposing effects on mRNA stability and translation provided a molecular mechanism for posttranscriptional control of c-fms expression.

    Evidence RNA immunoprecipitation, mRNA stability assays, polysome fractionation, competition binding assays in breast cancer cells

    PMID:20974809

    Open questions at the time
    • Whether this mechanism operates in primary macrophages not shown
    • Other RNA-binding proteins recognizing the c-fms 3′ UTR not surveyed
  12. 2013 High

    Whether CSF1R functions outside myeloid cells was controversial; conditional neuron-specific deletion showed CSF1R is expressed on hippocampal and cortical neurons and is neuroprotective during excitotoxic injury via CREB signaling, establishing a cell-autonomous neuronal role.

    Evidence Neuron-specific conditional CSF1R deletion, kainic acid excitotoxin model, CREB phosphorylation analysis

    PMID:23296467

    Open questions at the time
    • Which CSF1R ligand (CSF-1 vs IL-34) is the physiological neuronal agonist in vivo not resolved
    • Downstream signaling intermediates between CSF1R and CREB in neurons not mapped
  13. 2015 High

    Structure-based drug design of CSF1R inhibitors was enabled by co-crystallography; the PLX3397 co-crystal structure showed the inhibitor traps CSF1R in the autoinhibited conformation, providing a mechanistic rationale for selective kinase blockade.

    Evidence X-ray co-crystallography of CSF1R kinase domain with PLX3397, phase 1 clinical trial

    PMID:26222558

    Open questions at the time
    • Resistance mechanisms to PLX3397 not yet characterized
    • Whether JM-locking inhibitors differ functionally from activation-loop inhibitors not tested
  14. 2019 High

    The cis-regulatory architecture controlling tissue-specific CSF1R expression was incompletely understood; CRISPR deletion of the FIRE super-enhancer selectively ablated microglia and several tissue-resident macrophage populations while sparing monocytes, demonstrating lineage-specific enhancer dependence.

    Evidence CRISPR deletion of FIRE enhancer in mice, tissue macrophage quantification across multiple organs, in vitro ESC differentiation

    PMID:31324781

    Open questions at the time
    • Whether FIRE deletion affects macrophage function beyond abundance not assessed
    • Compensatory enhancer elements not surveyed
  15. 2019 High

    The molecular pathogenesis of HDLS/CSF1R-related leukoencephalopathy was mechanistically unclear; in vitro kinase assays of patient-derived mutations demonstrated defective autophosphorylation and reduced autophagy (LC3-II levels), linking kinase domain loss-of-function to disease.

    Evidence In vitro autophosphorylation assays of multiple mutant CSF1R proteins, LC3-II western blotting, patient sequencing

    PMID:31827782

    Open questions at the time
    • Whether reduced autophagy is a direct kinase substrate effect or secondary not determined
    • Microglial-specific consequences of individual mutations not characterized in vivo
  16. 2020 High

    How surface CSF1R abundance is regulated post-endocytically was poorly understood; two studies showed Rab11A and Rab11B promote lysosomal degradation of c-Fms in osteoclasts by enlarging endosomal compartments and augmenting cathepsin activity, with chloroquine rescue confirming lysosomal dependence.

    Evidence Rab11A/Rab11B overexpression and silencing in RAW-D cells and BMMs, LAMP1/cathepsin quantification, chloroquine rescue, flow cytometry

    PMID:33142674 PMID:33302495

    Open questions at the time
    • Whether Rab11-mediated degradation operates in macrophage populations beyond osteoclasts not tested
    • Ubiquitin signals directing c-Fms to lysosomes not identified
  17. 2022 High

    Whether CSF1R can be engineered for inhibitor resistance without functional compromise was untested; the G795A gatekeeper-adjacent substitution conferred resistance to PLX3397/PLX5622 while preserving normal kinase function, enabling selective microglial replacement in vivo.

    Evidence CRISPR-engineered iPSC-derived microglia with G795A mutation, biochemical kinase assays, xenotransplantation into PLX3397-treated mice, transcriptomic profiling

    PMID:36584406

    Open questions at the time
    • Long-term consequences of G795A microglia engraftment not assessed
    • Whether G795A confers resistance to other CSF1R inhibitor scaffolds not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full-length structure of CSF1R encompassing the extracellular, transmembrane, and intracellular domains in both inactive and active states is lacking, and the precise mechanism by which ligand-induced extracellular dimerization releases juxtamembrane autoinhibition remains structurally unresolved.
  • Full-length ligand-bound receptor structure not available
  • How IL-34 versus CSF-1 binding differentially activates downstream pathways not mechanistically resolved
  • In vivo significance of neuronal CSF1R under non-excitotoxic conditions not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0016740 transferase activity 4 GO:0048018 receptor ligand activity 2
Localization
GO:0005886 plasma membrane 6 GO:0005764 lysosome 2 GO:0005768 endosome 2 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1266738 Developmental Biology 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 2
Partners
CSF1DAP12ELAVL1HDLBPLNKPAX5STAP2SYK

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1985 The c-fms proto-oncogene product is the receptor for CSF-1 (M-CSF): it is a 165-170 kDa transmembrane glycoprotein with intrinsic tyrosine kinase activity, expressed on mononuclear phagocytes, that specifically binds CSF-1 and undergoes tyrosine phosphorylation upon ligand binding in membrane preparations. Immunoprecipitation with anti-v-fms antisera, specific CSF-1 binding assay, immune complex kinase assay in membrane preparations Cell High 2408759
1987 Phosphorylation of Tyr969 in the C-terminal tail of c-fms negatively regulates receptor kinase activity; mutation to Phe969 (as in v-fms) activates oncogenic potential of c-fms when combined with CSF-1 expression, and the C-terminal tyrosine deletion is necessary but not sufficient alone for transformation. NIH 3T3 transformation assay with chimeric v-fms/c-fms constructs, cotransfection with CSF-1 cDNA, site-directed mutagenesis of Tyr969 to Phe969 Nature High 3027579
1987 Proviral insertion at the fim-2 locus (spanning the 5'-end of c-fms) results in high-level expression of a normal-sized c-fms mRNA, establishing c-fms activation by retroviral insertion as a mechanism in myeloblastic leukemias. Southern blotting, Northern blotting, proviral integration mapping in Friend MuLV-induced murine myeloblastic leukemias Nature Medium 3476856
1988 CSF-1R (c-fms product) is a member of the receptor tyrosine kinase family; its intracellular tyrosine kinase domain transduces CSF-1 signals for proliferation, survival, and differentiation of mononuclear phagocyte lineage cells; v-fms mutations alter kinase activity to provide ligand-independent growth signals. Biochemical characterization, kinase activity assays, v-fms/c-fms domain comparisons Journal of cellular biochemistry High 2852667
1989 c-fms mRNA levels are regulated posttranscriptionally by a labile stabilizing protein in both differentiating HL-60 cells and in mature human monocytes; the rate of c-fms gene transcription is unchanged upon TPA-induced differentiation or TPA-induced downregulation, but mRNA half-life is dramatically altered by cycloheximide. Nuclear run-on transcription assays, mRNA half-life measurements with cycloheximide treatment, Northern blotting Molecular and cellular biology High 2523515
1990 Activation of CSF-1R intracellular tyrosine kinase domain alone (without CSF-1) is sufficient to induce mitogenesis; a chimeric CD2 ectodomain–CSF-1R kinase domain receptor expressed in NIH 3T3 fibroblasts undergoes tyrosine phosphorylation, receptor downmodulation, and mitogenesis upon anti-CD2 antibody stimulation. Chimeric receptor expression in NIH 3T3 cells, anti-CD2 antibody stimulation, tyrosine phosphorylation assay, proliferation assay Molecular and cellular biology High 1691441
2003 The transcription factor AML1 (RUNX1) directly binds the c-FMS gene in normal cells; in t(8;21) leukemic cells, the AML1-ETO fusion protein binds extended sequences of the c-FMS intronic regulatory region and alters histone modification patterns and increases association of histone deacetylases, without irreversibly disrupting transcription factor binding. In vivo footprinting, chromatin immunoprecipitation (ChIP) in normal and t(8;21) leukemic cells The EMBO journal High 12773394
2004 During B-lymphopoiesis, c-fms chromatin is silenced in discrete steps: first transcription factor binding and RNA expression are lost, then nuclease accessibility decreases; even in mature B cells the locus remains poised and can be reactivated by conditional deletion of Pax5; de novo DNA methylation overlaps with an intronic antisense transcription unit. DNase I hypersensitivity assays, chromatin immunoprecipitation, bisulfite sequencing, conditional Pax5 deletion in B cells The EMBO journal High 15483629
2005 Imatinib inhibits the CSF-1R (c-fms) kinase at therapeutic concentrations; it inhibits c-fms tyrosine phosphorylation in macrophages and blocks M-CSF-induced proliferation of a cytokine-dependent cell line, without downregulating c-fms expression. Phosphorylation assays in macrophages, cytokine-dependent cell line proliferation assay Blood High 15637141
2006 Pax5 directly represses c-fms by being recruited to the c-fms locus, causing rapid loss of RNA polymerase II binding and then loss of transcription factor binding and DNase I hypersensitivity at all cis-regulatory elements; Pax5 targets the basal transcription machinery by interacting with a binding site within the major transcription start sites. Chromatin immunoprecipitation, DNase I hypersensitivity assays, conditional Pax5 expression system The EMBO journal High 16482219
2007 Crystal structure of the autoinhibited human c-Fms kinase domain at 2.7 Å resolution shows that the juxtamembrane (JM) domain binds a hydrophobic site adjacent to the ATP binding pocket, preventing the activation loop from adopting an active conformation; three JM-derived tyrosine residues drive autoinhibition, a mechanism shared with c-Kit and Flt3. X-ray crystallography at 2.7 Å resolution of the cytosolic kinase + juxtamembrane domain Journal of molecular biology High 17292918
2008 M-CSF binding to CSF-1R (c-Fms) in osteoclasts generates a signaling complex with phosphorylated DAP12 (ITAM adaptor) and Syk kinase; c-Fms Tyr559 (exclusive c-Src binding site) is required for DAP12/Syk signaling; deletion of DAP12 or Syk yields osteoclasts that fail to reorganize their cytoskeleton, and Syk SH2 domain and DAP12 ITAM tyrosines and transmembrane domain mediate this signaling. Co-immunoprecipitation, retroviral transduction of null precursors with wild-type/mutant DAP12 and Syk, cytoskeleton analysis, genetic knockout models Molecular cell High 18691974
2010 The adaptor protein Lnk binds directly to c-Fms (CSF-1R) via its PH domain independently of M-CSF stimulation; Lnk overexpression suppresses M-CSF-induced tyrosine phosphorylation of c-Fms and Akt activation, and inhibits M-CSF-induced macrophage migration; Lnk KO macrophages show enhanced and prolonged Akt phosphorylation but diminished Erk phosphorylation in response to M-CSF. Co-immunoprecipitation, Lnk knockout macrophages, clonogenic assays, western blotting of Akt/Erk phosphorylation, migration assays Journal of leukocyte biology High 20571037
2010 STAP-2 adaptor protein directly binds to the PH domain of c-Fms independent of M-CSF stimulation; STAP-2 overexpression suppresses M-CSF-induced c-Fms tyrosine phosphorylation and downstream Akt and ERK activation, and impairs M-CSF-induced macrophage migration. Co-immunoprecipitation, overexpression in Raw 264.7 macrophages, western blotting of phospho-c-Fms, phospho-Akt, phospho-ERK, wound-healing migration assay Biochemical and biophysical research communications Medium 17512498
2010 Vigilin binds a 69-nucleotide non-AU-rich sequence in the c-fms 3' UTR and competitively displaces HuR from this site; vigilin decreases c-fms mRNA stability and inhibits c-fms translation, whereas HuR stabilizes c-fms mRNA; the two proteins exert opposing effects on breast cancer cell motility and invasion. RNA immunoprecipitation, mRNA stability assays, polysome fractionation, competition binding assays, cell invasion/motility assays Molecular and cellular biology High 20974809
2013 CSF1R is expressed on a small subpopulation of hippocampal and cortical neurons under physiological conditions; excitotoxic injury markedly upregulates neuronal CSF1R expression; selective deletion of CSF1R in forebrain neurons exacerbates excitotoxin-induced neurodegeneration; CSF1 /IL-34 neuroprotection is accompanied by maintenance of CREB signaling in neurons. Lineage-tracing experiments, conditional neuron-specific CSF1R deletion, kainic acid excitotoxin model, CREB phosphorylation western blot, histological quantification The Journal of experimental medicine High 23296467
2015 X-ray co-crystallography guided development of PLX3397, a CSF1R inhibitor that traps the kinase in the autoinhibited conformation; structure-based design enables selective CSF1R blockade. X-ray co-crystallography of CSF1R kinase with PLX3397, phase 1 clinical trial The New England journal of medicine High 26222558
2016 Resistance to CSF-1R inhibition in recurrent GBM is driven by the tumor microenvironment; macrophage-derived IGF-1 activates PI3K pathway via tumor cell IGF-1R, and transplantation of resistant tumors re-establishes sensitivity to CSF-1R inhibition. Tumor transplantation experiments, IGF-1/IGF-1R pathway analysis, PI3K inhibitor combination therapy in mouse GBM model Science High 27199435
2019 Deletion of the fms-intronic regulatory element (FIRE) super-enhancer within the Csf1r locus selectively ablates CSF1R expression in specific tissue macrophage populations (brain microglia, skin, kidney, heart, peritoneum macrophages) and blocks macrophage development from embryonic stem cells, while leaving monocyte homeostasis largely unaffected. CRISPR/genomic deletion of FIRE in mice, tissue macrophage quantification, in vitro ESC differentiation assay Nature communications High 31324781
2019 CSF1R haploinsufficiency (loss-of-function mutations) causes hereditary diffuse leukoencephalopathy with spheroids (HDLS); mutations in the kinase domain lead to defective autophosphorylation; mutant CSF1R proteins show lower expression levels and reduced autophagy (decreased LC3-II levels) compared to wild-type. Next-generation sequencing, Sanger sequencing, in vitro autophosphorylation assays of mutant CSF1R proteins, western blotting of LC3-II, immunofluorescence Translational neurodegeneration High 31827782
2020 Rab11A negatively regulates osteoclastogenesis by promoting lysosomal degradation of c-fms and RANK surface receptors; Rab11A overexpression enlarges early endosomes and upregulates lysosomal activity (LAMP1, cathepsins B and D), leading to proteolytic degradation of c-fms; lysosomal inhibition by chloroquine rescues c-fms and RANK protein levels. Rab11A overexpression/silencing in RAW-D cells and BMMs, immunocytochemistry for endosomal markers, LAMP1 and cathepsin quantification, chloroquine rescue experiments, flow cytometry of surface c-fms Cells High 33142674
2020 Rab11b promotes lysosomal degradation of c-Fms and RANK surface receptors in osteoclasts; Rab11b overexpression enlarges early/late endosomes and augments lysosomal activity, reducing surface c-Fms abundance and attenuating NFATc-1 upstream signaling; chloroquine inhibition of lysosomal function rescues c-Fms levels. Rab11b overexpression in RAW-D cells and BMMs, immunocytochemistry, flow cytometry of surface c-Fms, chloroquine rescue, western blotting International journal of molecular sciences Medium 33302495
2022 A glycine to alanine substitution at position 795 (G795A) of human CSF1R confers resistance to multiple CSF1R inhibitors (PLX3397, PLX5622) without discernable gain or loss of CSF1R function; G795A-expressing macrophages engraft mouse brain during PLX3397 treatment and persist after cessation. Biochemical and cell-based kinase activity assays, CRISPR engineering of iPSC-derived microglia, xenotransplantation studies, gene expression profiling The Journal of experimental medicine High 36584406
2004 gp130-dependent ERK1/2 MAP kinase signaling positively regulates c-fms expression in macrophages; in gp130(ΔSTAT/ΔSTAT) macrophages, enhanced ERK1/2 activation correlates with elevated c-fms expression and increased M-CSF responsiveness, while gp130(Y757F/Y757F) macrophages with reduced ERK1/2 activation show decreased c-fms expression and reduced M-CSF-induced proliferation; an ERK1/2 inhibitor suppresses M-CSF-induced proliferation and c-fms expression. gp130 signaling mutant knock-in mouse macrophages, ERK1/2 phosphorylation assays, clonogenic assays, pharmacological ERK1/2 inhibition, western blotting of c-fms Molecular and cellular biology High 14749363

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nature medicine 1920 24056773
1985 The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell 1567 2408759
2017 Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy. Journal for immunotherapy of cancer 830 28716061
2007 Identification of clonogenic common Flt3+M-CSFR+ plasmacytoid and conventional dendritic cell progenitors in mouse bone marrow. Nature immunology 558 17922016
2016 The tumor microenvironment underlies acquired resistance to CSF-1R inhibition in gliomas. Science (New York, N.Y.) 548 27199435
2015 Structure-Guided Blockade of CSF1R Kinase in Tenosynovial Giant-Cell Tumor. The New England journal of medicine 448 26222558
1987 Transforming potential of the c-fms proto-oncogene (CSF-1 receptor). Nature 340 3027579
1985 Expression of the c-fms proto-oncogene during human monocytic differentiation. Nature 325 2409450
2019 Deletion of a Csf1r enhancer selectively impacts CSF1R expression and development of tissue macrophage populations. Nature communications 292 31324781
2005 Macrophage colony-stimulating factor receptor c-fms is a novel target of imatinib. Blood 240 15637141
2013 Colony-stimulating factor 1 receptor (CSF1R) signaling in injured neurons facilitates protection and survival. The Journal of experimental medicine 196 23296467
1990 Ovarian adenocarcinomas express fms-complementary transcripts and fms antigen, often with coexpression of CSF-1. The American journal of pathology 162 1695482
2019 PET imaging of microglia by targeting macrophage colony-stimulating factor 1 receptor (CSF1R). Proceedings of the National Academy of Sciences of the United States of America 152 30635412
2019 CSF1R- and SHP2-Inhibitor-Loaded Nanoparticles Enhance Cytotoxic Activity and Phagocytosis in Tumor-Associated Macrophages. Advanced materials (Deerfield Beach, Fla.) 151 31659802
2018 Colony-Stimulating Factor 1 Receptor (CSF1R) Regulates Microglia Density and Distribution, but Not Microglia Differentiation In Vivo. Cell reports 127 30067976
2022 CSF1R inhibitors are emerging immunotherapeutic drugs for cancer treatment. European journal of medicinal chemistry 121 36335744
1989 Posttranscriptional stabilization of c-fms mRNA by a labile protein during human monocytic differentiation. Molecular and cellular biology 111 2523515
1987 Frequent c-fms activation by proviral insertion in mouse myeloblastic leukaemias. Nature 110 3476856
2013 Haploinsufficiency of CSF-1R and clinicopathologic characterization in patients with HDLS. Neurology 108 24336230
2008 DAP12 couples c-Fms activation to the osteoclast cytoskeleton by recruitment of Syk. Molecular cell 105 18691974
2006 Conditional deletion of the colony stimulating factor-1 receptor (c-fms proto-oncogene) in mice. Genesis (New York, N.Y. : 2000) 98 16823860
2019 Phenotypic impacts of CSF1R deficiencies in humans and model organisms. Journal of leukocyte biology 96 31330095
2018 Il34-Csf1r Pathway Regulates the Migration and Colonization of Microglial Precursors. Developmental cell 95 30205037
2012 MRI characteristics and scoring in HDLS due to CSF1R gene mutations. Neurology 95 22843259
2019 Pharmacological inhibition of CSF1R by GW2580 reduces microglial proliferation and is protective against neuroinflammation and dopaminergic neurodegeneration. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 87 31914683
2019 Dual inhibition of CSF1R and MAPK pathways using supramolecular nanoparticles enhances macrophage immunotherapy. Biomaterials 82 31670078
2014 Pleiotropic effects of extended blockade of CSF1R signaling in adult mice. Journal of leukocyte biology 82 24652541
2018 Recent advances in colony stimulating factor-1 receptor/c-FMS as an emerging target for various therapeutic implications. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 81 29679908
2009 Antibody blockade of c-fms suppresses the progression of inflammation and injury in early diabetic nephropathy in obese db/db mice. Diabetologia 80 19466391
2017 Therapeutic effects of CSF1R-blocking antibodies in multiple myeloma. Leukemia 74 28626216
2022 Engineering an inhibitor-resistant human CSF1R variant for microglia replacement. The Journal of experimental medicine 73 36584406
2002 Macrophage accumulation at a site of renal inflammation is dependent on the M-CSF/c-fms pathway. Journal of leukocyte biology 68 12223521
2007 The 2.7 A crystal structure of the autoinhibited human c-Fms kinase domain. Journal of molecular biology 61 17292918
2004 Epigenetic silencing of the c-fms locus during B-lymphopoiesis occurs in discrete steps and is reversible. The EMBO journal 61 15483629
2008 The transcriptional regulation of the Colony-Stimulating Factor 1 Receptor (csf1r) gene during hematopoiesis. Frontiers in bioscience : a journal and virtual library 60 17981568
2010 c-Fms-mediated differentiation and priming of monocyte lineage cells play a central role in autoimmune arthritis. Arthritis research & therapy 58 20181277
2021 CSF1R-dependent macrophages control postnatal somatic growth and organ maturation. PLoS genetics 56 34081701
2021 Vimseltinib: A Precision CSF1R Therapy for Tenosynovial Giant Cell Tumors and Diseases Promoted by Macrophages. Molecular cancer therapeutics 55 34433663
2014 Inhibition of CSF-1R supports T-cell mediated melanoma therapy. PloS one 55 25110953
2003 Aberrant expression of HOXA9, DEK, CBL and CSF1R in acute myeloid leukemia. Leukemia & lymphoma 55 14738146
2022 CD66b-CD64dimCD115- cells in the human bone marrow represent neutrophil-committed progenitors. Nature immunology 54 35484408
2020 Loss of homeostatic microglial phenotype in CSF1R-related Leukoencephalopathy. Acta neuropathologica communications 54 32430064
2011 c-fms blockade reverses glomerular macrophage infiltration and halts development of crescentic anti-GBM glomerulonephritis in the rat. Laboratory investigation; a journal of technical methods and pathology 54 21519331
2003 Epigenetic consequences of AML1-ETO action at the human c-FMS locus. The EMBO journal 53 12773394
1988 Colony-stimulating factor-1 receptor (c-fms). Journal of cellular biochemistry 52 2852667
2006 The mechanism of repression of the myeloid-specific c-fms gene by Pax5 during B lineage restriction. The EMBO journal 51 16482219
2020 Zebrafish macrophage developmental arrest underlies depletion of microglia and reveals Csf1r-independent metaphocytes. eLife 49 32367800
2021 Targeting CSF1R Alone or in Combination with PD1 in Experimental Glioma. Cancers 48 34063518
2021 Magnetism-mediated targeting hyperthermia-immunotherapy in "cold" tumor with CSF1R inhibitor. Theranostics 48 34093858
2022 Silence of a dependence receptor CSF1R in colorectal cancer cells activates tumor-associated macrophages. Journal for immunotherapy of cancer 47 36600555
2021 Clinical Development of Colony-Stimulating Factor 1 Receptor (CSF1R) Inhibitors. Journal of immunotherapy and precision oncology 47 35663534
2008 An anti-c-Fms antibody inhibits orthodontic tooth movement. Journal of dental research 47 18362327
2011 Mouse blood monocytes: standardizing their identification and analysis using CD115. Journal of immunological methods 45 21466808
2005 Inhibition of c-fms by imatinib: expanding the spectrum of treatment. Cell cycle (Georgetown, Tex.) 45 15917650
2021 Treatment of CSF1R-Related Leukoencephalopathy: Breaking New Ground. Movement disorders : official journal of the Movement Disorder Society 43 34329526
1990 IL-2 enhances c-fms expression in human monocytes. Journal of immunology (Baltimore, Md. : 1950) 39 2143208
2004 Imbalanced gp130-dependent signaling in macrophages alters macrophage colony-stimulating factor responsiveness via regulation of c-fms expression. Molecular and cellular biology 37 14749363
2020 Small-molecule CSF1R kinase inhibitors; review of patents 2015-present. Expert opinion on therapeutic patents 36 33108917
1994 The expression of FMS, KIT and FLT3 in hematopoietic malignancies. Leukemia & lymphoma 36 7519507
2013 LPS converts Gr-1(+)CD115(+) myeloid-derived suppressor cells from M2 to M1 via P38 MAPK. Experimental cell research 35 23701951
2024 Insights into CSF-1R Expression in the Tumor Microenvironment. Biomedicines 33 39457693
2023 The RNA m6A demethylase ALKBH5 drives emergency granulopoiesis and neutrophil mobilization by upregulating G-CSFR expression. Cellular & molecular immunology 33 38114747
2019 Mechanically Defined Microenvironment Promotes Stabilization of Microvasculature, Which Correlates with the Enrichment of a Novel Piezo-1+ Population of Circulating CD11b+ /CD115+ Monocytes. Advanced materials (Deerfield Beach, Fla.) 33 30924979
2010 Posttranscriptional suppression of proto-oncogene c-fms expression by vigilin in breast cancer. Molecular and cellular biology 33 20974809
2012 FMS Kinase Inhibitors: Current Status and Future Prospects. Medicinal research reviews 32 22434539
2020 Small-Molecule CSF1R Inhibitors as Anticancer Agents. Current medicinal chemistry 31 31215373
2020 G-CSF and G-CSFR Induce a Pro-Tumorigenic Macrophage Phenotype to Promote Colon and Pancreas Tumor Growth. Cancers 31 33036138
2013 A unique anti-CD115 monoclonal antibody which inhibits osteolysis and skews human monocyte differentiation from M2-polarized macrophages toward dendritic cells. mAbs 31 23924795
2019 Clinicopathologic characterization and abnormal autophagy of CSF1R-related leukoencephalopathy. Translational neurodegeneration 30 31827782
2013 E3 ubiquitin ligase Fbw7 negatively regulates granulocytic differentiation by targeting G-CSFR for degradation. Biochimica et biophysica acta 30 23820376
1990 The role of the c-fms oncogene in the regulation of HL-60 cell differentiation. Oncogene 30 2141686
2019 Characterization of Subpopulations of Chicken Mononuclear Phagocytes That Express TIM4 and CSF1R. Journal of immunology (Baltimore, Md. : 1950) 29 30626692
2019 G-CSFR antagonism reduces neutrophilic inflammation during pneumococcal and influenza respiratory infections without compromising clearance. Scientific reports 29 31776393
2024 CSF-1R in Cancer: More than a Myeloid Cell Receptor. Cancers 27 38254773
2018 A dual-specific macrophage colony-stimulating factor antagonist of c-FMS and αvβ3 integrin for osteoporosis therapy. PLoS biology 27 30142160
2010 Adaptor protein Lnk inhibits c-Fms-mediated macrophage function. Journal of leukocyte biology 25 20571037
2011 Anti-c-Fms antibody inhibits lipopolysaccharide-induced osteoclastogenesis in vivo. FEMS immunology and medical microbiology 24 22067001
2020 Inhibition of CSF1R and AKT by (±)-kusunokinin hinders breast cancer cell proliferation. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 22 32535390
1995 Regulation of the c-fms promoter in murine tumour cell lines. Oncogene 22 7478559
1993 CSF-1 control of C-FMS expression in normal human bone marrow progenitors. Journal of cellular physiology 22 8482721
2021 Clinical and genetic characterization of adult-onset leukoencephalopathy caused by CSF1R mutations. Annals of clinical and translational neurology 21 34652888
2019 Establishment of an orthodontic retention mouse model and the effect of anti-c-Fms antibody on orthodontic relapse. PloS one 21 31216288
2024 The Phenotypic and Genotypic Spectrum of CSF1R-Related Disorder in China. Movement disorders : official journal of the Movement Disorder Society 20 38465843
2020 SWATH-Proteomics of Ibrutinib's Action in Myeloid Leukemia Initiating Mutated G-CSFR Signaling. Proteomics. Clinical applications 20 32319217
2024 Deplete and repeat: microglial CSF1R inhibition and traumatic brain injury. Frontiers in cellular neuroscience 19 38450286
2021 G-CSFR antagonism reduces mucosal injury and airways fibrosis in a virus-dependent model of severe asthma. British journal of pharmacology 19 33609280
2020 Rab11A Functions as a Negative Regulator of Osteoclastogenesis through Dictating Lysosome-Induced Proteolysis of c-fms and RANK Surface Receptors. Cells 19 33142674
2007 STAP-2 regulates c-Fms/M-CSF receptor signaling in murine macrophage Raw 264.7 cells. Biochemical and biophysical research communications 19 17512498
2024 CSF1R-Related Disorder: Prevalence of CSF1R Variants and Their Clinical Significance in the UK Population. Neurology. Genetics 18 39040919
2012 Defective G-CSFR signaling pathways in congenital neutropenia. Hematology/oncology clinics of North America 18 23351989
2013 An anti-c-Fms antibody inhibits osteoclastogenesis in a mouse periodontitis model. Oral diseases 17 23651419
2009 CSF-1R, DAP12 and beta-catenin: a ménage à trois. Nature immunology 17 19536190
2009 An M-CSF receptor c-Fms antibody inhibits mechanical stress-induced root resorption during orthodontic tooth movement in mice. The Angle orthodontist 17 19705931
1990 Antibody-induced mitogenicity mediated by a chimeric CD2-c-fms receptor. Molecular and cellular biology 17 1691441
2021 Effect of CSF1R inhibitor on glial cells population and remyelination in the cuprizone model. Neuropeptides 16 34274854
2020 Discovery of IACS-9439, a Potent, Exquisitely Selective, and Orally Bioavailable Inhibitor of CSF1R. Journal of medicinal chemistry 16 32787110
2022 M-CSFR/CSF1R signaling regulates myeloid fates in zebrafish via distinct action of its receptors and ligands. Blood advances 15 34979548
2020 The Inhibitory Role of Rab11b in Osteoclastogenesis through Triggering Lysosome-Induced Degradation of c-Fms and RANK Surface Receptors. International journal of molecular sciences 15 33302495
2019 Lipoxin-Induced Phenotypic Changes in CD115+LY6Chi Monocytes TAM Precursors Inhibits Tumor Development. Frontiers in oncology 15 31275860
2016 Resident corneal c-fms(+) macrophages and dendritic cells mediate early cellular infiltration in adenovirus keratitis. Experimental eye research 15 27185163