Affinage

CSF1R

Macrophage colony-stimulating factor 1 receptor · UniProt P07333

Length
972 aa
Mass
108.0 kDa
Annotated
2026-06-09
100 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CSF1R (c-Fms) is the 170 kDa glycoprotein class III receptor tyrosine kinase of the mononuclear phagocyte lineage that binds CSF-1 (M-CSF), undergoes ligand-induced tyrosine autophosphorylation, and transduces signals controlling the survival, proliferation, differentiation, and migration of macrophages and osteoclasts (PMID:2408759, PMID:3027579). Ligand engagement activates downstream PI3K/AKT and ERK1/2 cascades (PMID:17512498, PMID:31636099), and discrete cytoplasmic tyrosines parse distinct outputs: Y559 is the c-Src binding site required to assemble a DAP12/Syk signaling complex driving cytoskeletal reorganization in osteoclasts, while Y697 is the residue critical for ERK/c-Fos osteoclastogenic signaling shared with αvβ3 integrin (PMID:18691974, PMID:12618529); a C-terminal Tyr969 acts as a negative regulator whose mutation to Phe enhances oncogenic potential (PMID:3027579). Receptor output is restrained at multiple levels: the adaptors STAP-2 and Lnk bind c-Fms and blunt M-CSF-induced AKT/ERK activation and macrophage migration (PMID:17512498, PMID:20571037), and iRhom2/ADAM17-mediated ectodomain shedding limits cell-surface receptor accumulation (PMID:27601030). Expression is controlled post-transcriptionally by a labile protein that stabilizes c-fms mRNA (PMID:2523515) and transcriptionally by the conserved intronic super-enhancer FIRE, whose deletion selectively ablates CSF1R and macrophage development in brain, skin, kidney, heart, and peritoneum (PMID:31324781). In development, IL-34 acting through CSF1R directs microglial precursor colonization of the CNS (PMID:30205037), and a dominant kinase-dead CSF1R mutation modeling human ALSP reduces microglial number and arborization (PMID:35333324). CSF1R kinase is druggable by inhibitors including PLX3397, which traps the receptor in its autoinhibited conformation (PMID:26222558), and CSF1R-targeted therapy is being exploited across osteolytic, glioma, and lymphoma settings, with characterized resistance mechanisms via microenvironmental IGF-1/IGF-1R/PI3K signaling and a G795A gatekeeper substitution (PMID:27199435, PMID:31636099, PMID:36584406).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1985 High

    Established the molecular identity of the CSF-1 receptor by showing the c-fms proto-oncogene product is a glycoprotein tyrosine kinase that directly binds CSF-1, resolving whether the receptor and the oncogene product were the same molecule.

    Evidence Immune complex kinase assay, radioligand binding, and cross-reactive antisera in mononuclear phagocyte membranes

    PMID:2408759

    Open questions at the time
    • Specific autophosphorylation sites and downstream effectors not yet mapped
    • Ligand IL-34 not yet known
  2. 1987 High

    Showed CSF1R signaling is sufficient to confer growth responsiveness and identified the C-terminal Tyr969 as an intrinsic negative regulator whose loss potentiates transformation, defining a built-in autoinhibitory brake.

    Evidence NIH 3T3 cotransfection transformation assay with Tyr969→Phe chimeric mutants

    PMID:3027579

    Open questions at the time
    • Mechanism by which Tyr969 suppresses kinase activity not resolved
    • Adaptor proteins binding Tyr969 not identified
  3. 1989 High

    Distinguished transcriptional from post-transcriptional control of CSF1R, showing receptor mRNA abundance during differentiation is governed by a labile protein that stabilizes the transcript rather than by transcription rate.

    Evidence Nuclear run-on, cycloheximide chase, and Northern blotting in HL-60 cells and monocytes

    PMID:2523515

    Open questions at the time
    • Identity of the stabilizing labile protein unknown
    • cis-acting mRNA element not mapped
  4. 2003 High

    Assigned a specific cytoplasmic tyrosine (Y697) to ERK/c-Fos osteoclastogenic signaling and its functional collaboration with αvβ3 integrin, beginning the parsing of CSF1R outputs by residue.

    Evidence Retroviral transduction of cytoplasmic-domain mutants into primary osteoclast precursors with ERK and differentiation rescue in β3-null cells

    PMID:12618529

    Open questions at the time
    • Direct effectors recruited to Y697 not defined
    • Generality beyond osteoclasts untested
  5. 2008 High

    Defined the Y559–c-Src–DAP12/Syk axis required for CSF1R-driven cytoskeletal reorganization, establishing how the receptor couples to an ITAM adaptor module in osteoclasts.

    Evidence Reconstitution of null precursors with mutant DAP12/Syk, reciprocal co-IP, and site-directed mutagenesis of Y559 and ITAM residues

    PMID:18691974

    Open questions at the time
    • Stoichiometry of the c-Fms/DAP12/Syk complex not resolved
    • Whether the same module operates in non-osteoclast macrophages unclear
  6. 2010 Medium

    Identified negative regulators STAP-2 and Lnk that directly bind c-Fms and attenuate M-CSF-induced AKT/ERK signaling and macrophage migration, revealing adaptor-mediated dampening of the receptor.

    Evidence Co-IP, knockout/overexpression with AKT/ERK phosphorylation and migration/clonogenic readouts (idx 7, 9)

    PMID:17512498 PMID:20571037

    Open questions at the time
    • Binding sites on c-Fms not fully mapped for both adaptors
    • Single-lab studies without reciprocal cross-validation
  7. 2016 Medium

    Established that ectodomain shedding by the iRhom2/ADAM17 pathway limits surface CSF1R, adding a proteolytic layer of receptor regulation that controls myeloid repopulation capacity.

    Evidence Degradomics screen plus iRhom2-/- mice and competitive bone marrow chimera assays

    PMID:27601030

    Open questions at the time
    • Cleavage site and shed fragment fate not characterized
    • Single-lab finding
  8. 2019 High

    Demonstrated transcriptional control of CSF1R by the conserved FIRE super-enhancer, showing tissue-selective dependence of macrophage development on this regulatory element.

    Evidence CRISPR deletion of FIRE in mice with comprehensive tissue macrophage flow cytometry and reporter analysis

    PMID:31324781

    Open questions at the time
    • Transcription factors acting at FIRE not identified
    • Why monocytes lack surface CSF1R despite normal numbers unexplained
  9. 2018 High

    Showed IL-34 acting through CSF1R guides microglial precursor migration into the CNS during development, separating brain colonization from peripheral macrophage seeding.

    Evidence Zebrafish il34 and csf1ra loss- and gain-of-function with live imaging of macrophage migration

    PMID:30205037

    Open questions at the time
    • Downstream migratory effectors not defined
    • Relative contribution of CSF-1 vs IL-34 in mammalian CNS not addressed here
  10. 2022 High

    Linked CSF1R kinase activity to neurodevelopmental disease by showing a dominant-negative kinase-dead mutation reduces microglial numbers, contrasting with the microgliosis of haploinsufficiency.

    Evidence CRISPR knock-in Csf1rE631K mice with CSF1 stimulation assays, CSF1-Fc in vivo, and microglial morphology versus Csf1r+/- mice

    PMID:35333324

    Open questions at the time
    • Molecular basis of the dominant-negative effect on wild-type receptor not detailed
    • Human ALSP genotype-phenotype correlation not directly tested
  11. 2016 High

    Resolved how CSF1R kinase inhibitors work structurally and how tumors evade them, mapping a druggable autoinhibited conformation and a microenvironmental IGF-1/IGF-1R/PI3K resistance route.

    Evidence X-ray co-crystallography of CSF1R with PLX3397 (idx 11) and transplantation/phosphoproteomic resistance analysis in glioma (idx 12)

    PMID:26222558 PMID:27199435

    Open questions at the time
    • Generalizability of IGF-1 resistance across tumor types not established
    • Structural basis of resistance mutations not in these studies
  12. 2022 High

    Engineered a CSF1R gatekeeper variant (G795A) that resists inhibitors without altering receptor function, enabling inhibitor-protected microglia replacement and providing a tool to dissect on-target inhibitor effects.

    Evidence CRISPR-engineered iPSC-derived microglia (G795A) xenotransplanted into PLX3397-treated mice with biochemical and inflammatory profiling

    PMID:36584406

    Open questions at the time
    • Structural mechanism of G795A inhibitor resistance not solved here
    • Long-term safety of replacement microglia unassessed
  13. 2020 Medium

    Proposed a context-dependent dependence-receptor role for CSF1R on cancer cells, where caspase cleavage restrains tumor growth but ligand redirection to TAMs promotes progression when receptor is silenced.

    Evidence Reconstitution/knockdown in CRC cells, caspase cleavage assay, and macrophage co-culture with in vivo tumor growth

    PMID:36600555

    Open questions at the time
    • Caspase cleavage site and pro-death signaling not mapped
    • Single-lab, novel mechanism awaiting independent confirmation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CSF1R signaling outputs are quantitatively integrated across the diverse macrophage lineages and disease contexts—and the molecular identity of post-transcriptional and FIRE-acting regulators—remains unresolved.
  • Stabilizing labile mRNA-binding protein unidentified
  • Transcription factors at FIRE undefined
  • Unified model relating residue-specific signaling to cell-type-specific outcomes lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 4 GO:0140096 catalytic activity, acting on a protein 3 GO:0060089 molecular transducer activity 2 GO:0048018 receptor ligand activity 1
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3
Partners
ADAM17CSF1DAP12IL34LNKSRCSTAP2SYK

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1985 The c-fms proto-oncogene product is a 170 kDa glycoprotein with associated tyrosine kinase activity that specifically binds CSF-1 (M-CSF) and is phosphorylated on tyrosine in the presence of CSF-1; the murine c-fms product and the CSF-1 receptor are related or identical molecules restricted to cells of the mononuclear phagocyte lineage. Immune complex kinase assay, radioligand binding (CSF-1 binding), tyrosine phosphorylation in membrane preparations, cross-reactive antisera to v-fms-coded polypeptide Cell High 2408759
1987 CSF1R (c-fms) transduction of growth signals is sufficient to confer CSF-1-responsive growth in NIH 3T3 cells. A C-terminal tyrosine residue (Tyr969) acts as a negative regulator of receptor kinase activity; its replacement by Phe969 activates oncogenic potential in conjunction with CSF-1 or other mutations, but is not sufficient alone for transformation. NIH 3T3 cotransfection transformation assay, chimeric v-fms/c-fms constructs with point mutations (Tyr969→Phe969), anchorage-independent growth assays Nature High 3027579
1988 CSF1R (c-fms) encodes the receptor for CSF-1 with an intrinsic tyrosine-specific protein kinase activity; ligand binding stimulates kinase activity, and constitutive activation (as in v-fms) or removal of the negative-regulatory C-terminal Tyr969 provides growth signals in the absence of ligand. Biochemical review synthesizing kinase assays, mutagenesis, and transformation data Journal of cellular biochemistry Medium 2852667
1989 c-fms mRNA levels are regulated post-transcriptionally by a labile protein that stabilizes the transcript; transcription rate is unchanged during monocytic differentiation or TPA-induced down-regulation, but the half-life of c-fms mRNA changes from >6 h to ~30 min when protein synthesis is inhibited. Nuclear run-on transcription assay, cycloheximide chase (mRNA half-life), Northern blotting in HL-60 cells and human monocytes Molecular and cellular biology High 2523515
2003 During osteoclastogenesis, c-Fms collaborates with αvβ3 integrin via shared activation of the ERK/c-Fos signaling pathway; normalization of osteoclastogenesis and ERK activation in β3-null cells uniquely requires c-Fms tyrosine 697, identifying this residue as the critical signaling site. Retroviral transduction of chimeric c-Fms constructs with cytoplasmic domain mutations into primary osteoclast precursors; ERK phosphorylation assays; osteoclast differentiation rescue experiments in β3-/- cells The Journal of clinical investigation High 12618529
2005 Imatinib inhibits c-Fms (CSF1R) kinase activity at therapeutic concentrations, blocking CSF-1-induced phosphorylation of c-Fms and M-CSF-dependent proliferation; this is not due to reduced c-fms expression. Phosphorylation inhibition assay (c-Fms phosphorylation in cells), M-CSF-dependent proliferation assay in cytokine-dependent cell line, Western blot for c-fms expression Blood Medium 15637141
2006 M-CSF binding to c-Fms triggers downstream signaling in osteoclasts including ERK activation; pharmacological inhibition of c-Fms kinase (Ki20227, IC50 = 2 nM) suppresses osteoclast differentiation and osteolytic bone destruction in vivo. In vitro kinase assay (IC50 determination), TRAP+ osteoclast formation assay in mouse bone marrow, in vivo bone metastasis/osteolysis model in nude rats, ovariectomy model Molecular cancer therapeutics Medium 17121910
2007 STAP-2 (signal-transducing adaptor protein-2) directly binds to the PH-domain interaction site on c-Fms independently of M-CSF stimulation, suppresses M-CSF-induced tyrosine phosphorylation of c-Fms and downstream Akt and ERK activation, and inhibits M-CSF-induced macrophage migration. Co-immunoprecipitation (STAP-2 PH domain interaction with c-Fms), Western blot for c-Fms phosphorylation, Akt/ERK activation assays, macrophage migration/wound-healing assay in Raw 264.7 overexpressing STAP-2 Biochemical and biophysical research communications Medium 17512498
2008 M-CSF binding to c-Fms generates a signaling complex comprising phosphorylated DAP12 (ITAM adaptor) and the non-receptor tyrosine kinase Syk in osteoclasts; c-Fms tyrosine 559 (the exclusive c-Src binding site) is required for DAP12/Syk activation and cytoskeletal reorganization; the SH2 domain of Syk and ITAM tyrosines plus transmembrane domain of DAP12 mediate the signal. Co-immunoprecipitation of DAP12/Syk complex, retroviral transduction of null precursors with wild-type or mutant DAP12/Syk, site-directed mutagenesis (c-Fms Y559, DAP12 ITAM tyrosines and transmembrane domain), cytoskeletal reorganization assay Molecular cell High 18691974
2010 The SH2-domain adaptor protein Lnk binds to c-Fms, blunts M-CSF-stimulated Akt phosphorylation (while diminishing ERK phosphorylation), reduces M-CSF-dependent macrophage migration, and restrains M-CSF-driven clonogenic macrophage progenitor expansion. Co-immunoprecipitation (Lnk binding to c-Fms), Lnk-knockout mouse bone marrow clonogenic assay, Western blot for Akt/ERK phosphorylation, macrophage migration assay Journal of leukocyte biology Medium 20571037
2012 In Nf1 haploinsufficient osteoclast progenitors, M-CSF binding to c-Fms results in increased c-Fms activation and downstream hyperactivation of Erk1/2 and p90RSK, mediating gain-of-function in migration, adhesion, and bone resorption; selective c-Fms inhibition (PLX3397) attenuates these phenotypes and prevents bone loss in vivo. c-Fms phosphorylation assay, Erk1/2/p90RSK activation Western blot, migration/adhesion/pit-formation assays, PLX3397 pharmacological inhibition, in vivo OVX mouse model with micro-CT PloS one Medium 23144792
2015 X-ray co-crystallography revealed that PLX3397 inhibits CSF1R kinase by trapping the receptor in its autoinhibited conformation; this structure-guided inhibitor is potent and selective for CSF1R. X-ray co-crystallography of CSF1R kinase domain with PLX3397, structure-guided medicinal chemistry The New England journal of medicine High 26222558
2016 Acquired resistance to CSF-1R inhibition in recurrent glioma is driven by the tumor microenvironment: macrophage-derived IGF-1 activates PI3K pathway via tumor cell IGF-1R, and this resistance is reversible upon tumor transplantation, establishing an epistatic tumor microenvironment→IGF-1/IGF-1R→PI3K pathway. Transplantation experiments (resistance reversibility), phosphoproteomic/gene expression analysis of recurrent vs. primary GBM, IGF-1R/PI3K inhibitor combination studies in vivo Science (New York, N.Y.) High 27199435
2016 iRhom2/ADAM17 pathway regulates CSF1R shedding from the myeloid cell surface; loss of iRhom2 leads to constitutive accumulation of membrane-bound CSF1R, enhanced CSF1R signaling, and competitive repopulation advantage of monocytes, macrophages, and dendritic cells. Degradomics screen (unbiased), iRhom2-/- mouse analysis by flow cytometry, mixed bone marrow chimera competitive repopulation assay, in vitro LSK cell growth in response to CSF1 European journal of immunology Medium 27601030
2018 IL-34 signals through Csf1ra (the CSF1R ortholog in zebrafish) to attract microglial precursors to the brain during embryogenesis; in il34- or csf1ra-deficient zebrafish, embryonic macrophages fail to migrate to the anterior head and colonize the CNS, while peripheral tissue colonization is unaffected. Zebrafish genetic loss-of-function (il34 and csf1ra mutants), live imaging of macrophage migration, gain-of-function (exogenous Il34 activation), comparison of CNS vs. peripheral tissue colonization Developmental cell High 30205037
2019 Deletion of FIRE (fms-intronic regulatory element), a conserved super-enhancer within the Csf1r locus, selectively ablates CSF1R expression and macrophage development in specific tissues (brain microglia, skin, kidney, heart, peritoneum) without affecting monocytes or other macrophage populations; monocytes lack surface CSF1R protein despite normal monocyte numbers. CRISPR genomic deletion of FIRE enhancer in mice, flow cytometry for tissue macrophage populations, embryonic stem cell macrophage differentiation assay, reporter expression analysis Nature communications High 31324781
2019 CSF1R signaling is activated by CSF1 in T-cell lymphoma cells in an autocrine/paracrine manner leading to CSF1R autophosphorylation, and downstream activation of PI3K/AKT/mTOR signaling pathway; loss-of-function (pexidartinib inhibition and genetic knockdown) reduces T-cell lymphoma growth in vitro and in vivo. CSF1R autophosphorylation assays, phosphoproteomic and genomic screening, pharmacological inhibition (pexidartinib), loss-of-function in vitro and in vivo mouse models Clinical cancer research Medium 31636099
2019 CSF1R is expressed on F4/80hi Kupffer cells (KCs); Csf1r inhibition reduces F4/80hi KCs by ~50% without affecting CD11bhi KCs, delays liver regeneration after partial hepatectomy, increases hepatic injury, and attenuates KC cytokine responses to stimulation. Flow cytometry of KC subsets, Csf1r-GFP reporter mice, pharmacological CSF1R inhibition in partial hepatectomy model, liver-to-body weight ratio, serum ALT, proliferation assays, in vitro KC cytokine assays PloS one Medium 31042769
2020 CSF1R in colorectal cancer cells acts as a dependence receptor: when expressed on cancer cells, CSF1R is cleaved by caspases and constrains tumor growth (tumor suppressor function); when silenced on cancer cells, its ligands are redirected to stimulate CSF1R on M2 tumor-associated macrophages, promoting tumor progression. CSF1R reconstitution/overexpression in CRC cells, caspase cleavage assay, siRNA knockdown, co-culture competition system (CRC cells vs. macrophages), in vitro and in vivo tumor growth assays Journal for immunotherapy of cancer Medium 36600555
2022 A kinase-dead CSF1R point mutation (E631K in mouse, modeling human ALSP-associated mutations) acts dominantly to inhibit CSF1R signaling: heterozygous Csf1rE631K/+ mice are unresponsive to CSF1 stimulation in vitro and to exogenous CSF1-Fc in vivo, and show reduced microglial numbers and dendritic arborisation, opposite to Csf1r+/- haploinsufficiency microgliosis. Knock-in mouse model (CRISPR), bone marrow cell stimulation assay, CSF1-Fc fusion protein in vivo administration, flow cytometry and morphological analysis of microglia, comparison with Csf1r+/- mice Development (Cambridge, England) High 35333324
2022 A glycine-to-alanine substitution at position 795 of human CSF1R (G795A) confers resistance to multiple CSF1R inhibitors (PLX3397, PLX5622) without discernible gain or loss of receptor function; G795A-expressing macrophages can engraft and persist in PLX3397-treated mouse brains, enabling nontoxic microglia replacement. Biochemical and cell-based functional assays (no gain/loss of function determination), xenotransplantation of CRISPR-engineered iPSC-derived microglia (G795A) into PLX3397-treated mice, gene expression profiling, inflammatory response assays The Journal of experimental medicine High 36584406
1994 c-Fms (CSF1R) and c-Kit operate in a functional hierarchy during bone marrow macrophage progenitor (CFU-M) production: c-Kit plays the primary role in CFU-M production and maintenance (anti-c-Kit depletes CFU-M in vivo), while c-Fms, although co-expressed with c-Kit and functional in culture, has minimal role in CFU-M proliferation in the bone marrow in vivo. Antagonistic monoclonal antibody to murine c-Fms, anti-c-Kit mAb injection in vivo, flow cytometric sorting of c-Kit+c-Fms- vs. c-Kit+c-Fms+ fractions, CFU-M clonogenic assay Oncogene Medium 8545103
1994 CSF-1 (M-CSF) binding to c-Fms (CSF1R) on hairy cell leukemia cells induces chemokinetic and chemotactic cell movement, actin polymerization/redistribution, and cell morphology changes; this motility is modulated by αvβ3 integrin function. Video microscopy, image analysis, migration assays, F-actin staining, integrin function assays Blood Medium 8118039
2009 TGF-β1 induces c-fms (CSF1R) mRNA and cell-surface protein expression in endometrial epithelial cells, and TGF-β1-induced transmesothelial invasion is inhibited by TGF-β antagonists, linking TGF-β signaling to c-fms upregulation and invasive behavior. Real-time RT-PCR for c-fms mRNA, flow cytometry for cell-surface c-fms, 3D transmesothelial invasion assay, TGF-β pathway antagonism Molecular human reproduction Low 19505996
2022 CSF1/CSF1R signaling in cancer-associated fibroblasts leads to MIP-2 (CXCL2) secretion, which acts via CXCR2 on macrophages to induce suppressive and angiogenic properties; CSF1R+ macrophages promote pleural fluid accumulation by enhancing vascular permeability and destabilizing tumor vessels. Mice with CSF1R-deficient macrophages (genetic model), BLZ945 pharmacological CSF1R inhibition, vascular permeability assays, in vivo MPE models, cell-cell interaction analysis JCI insight Medium 35315360

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 1953 24056773
1985 The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell 1568 2408759
2017 Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy. Journal for immunotherapy of cancer 846 28716061
2016 The tumor microenvironment underlies acquired resistance to CSF-1R inhibition in gliomas. Science (New York, N.Y.) 563 27199435
2007 Identification of clonogenic common Flt3+M-CSFR+ plasmacytoid and conventional dendritic cell progenitors in mouse bone marrow. Nature immunology 559 17922016
2015 Structure-Guided Blockade of CSF1R Kinase in Tenosynovial Giant-Cell Tumor. The New England journal of medicine 454 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 303 31324781
2005 Macrophage colony-stimulating factor receptor c-fms is a novel target of imatinib. Blood 240 15637141
1983 Transcription of c-onc genes c-rasKi and c-fms during mouse development. Molecular and cellular biology 189 6308423
1989 Expression of the c-fms proto-oncogene and of the cytokine, CSF-1, during mouse embryogenesis. Developmental biology 175 2523324
2018 CSF1R-related leukoencephalopathy: A major player in primary microgliopathies. Neurology 167 30429277
1995 Functional hierarchy of c-kit and c-fms in intramarrow production of CFU-M. Oncogene 155 8545103
2019 CSF1R- and SHP2-Inhibitor-Loaded Nanoparticles Enhance Cytotoxic Activity and Phagocytosis in Tumor-Associated Macrophages. Advanced materials (Deerfield Beach, Fla.) 154 31659802
2003 c-Fms and the alphavbeta3 integrin collaborate during osteoclast differentiation. The Journal of clinical investigation 154 12618529
1988 Expression of the macrophage colony-stimulating factor and c-fms genes in human acute myeloblastic leukemia cells. The Journal of clinical investigation 140 2832442
2006 M-CSF, c-Fms, and signaling in osteoclasts and their precursors. Annals of the New York Academy of Sciences 132 16831911
2022 CSF1R inhibitors are emerging immunotherapeutic drugs for cancer treatment. European journal of medicinal chemistry 131 36335744
2018 Colony-Stimulating Factor 1 Receptor (CSF1R) Regulates Microglia Density and Distribution, but Not Microglia Differentiation In Vivo. Cell reports 130 30067976
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
2008 DAP12 couples c-Fms activation to the osteoclast cytoskeleton by recruitment of Syk. Molecular cell 106 18691974
2018 Il34-Csf1r Pathway Regulates the Migration and Colonization of Microglial Precursors. Developmental cell 100 30205037
2019 Phenotypic impacts of CSF1R deficiencies in humans and model organisms. Journal of leukocyte biology 98 31330095
2012 MRI characteristics and scoring in HDLS due to CSF1R gene mutations. Neurology 96 22843259
1992 Expression of CSF-1/c-fms and SF/c-kit mRNA during preimplantation mouse development. Developmental biology 90 1374350
2017 CSF-1R Inhibitor Development: Current Clinical Status. Current oncology reports 89 28875266
2006 A c-fms tyrosine kinase inhibitor, Ki20227, suppresses osteoclast differentiation and osteolytic bone destruction in a bone metastasis model. Molecular cancer therapeutics 87 17121910
2022 Targeting CSF-1R represents an effective strategy in modulating inflammatory diseases. Pharmacological research 86 36423789
2019 Dual inhibition of CSF1R and MAPK pathways using supramolecular nanoparticles enhances macrophage immunotherapy. Biomaterials 83 31670078
2018 Recent advances in colony stimulating factor-1 receptor/c-FMS as an emerging target for various therapeutic implications. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 82 29679908
1988 c-fms expression is a molecular marker of human acute myeloid leukemias. Blood 79 2970873
2022 Engineering an inhibitor-resistant human CSF1R variant for microglia replacement. The Journal of experimental medicine 75 36584406
2017 Therapeutic effects of CSF1R-blocking antibodies in multiple myeloma. Leukemia 74 28626216
2016 CSF1R mosaicism in a family with hereditary diffuse leukoencephalopathy with spheroids. Brain : a journal of neurology 69 27190017
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
2020 Loss of homeostatic microglial phenotype in CSF1R-related Leukoencephalopathy. Acta neuropathologica communications 56 32430064
2022 CD66b-CD64dimCD115- cells in the human bone marrow represent neutrophil-committed progenitors. Nature immunology 55 35484408
2003 Aberrant expression of HOXA9, DEK, CBL and CSF1R in acute myeloid leukemia. Leukemia & lymphoma 55 14738146
2019 Colony-Stimulating Factor 1 Receptor (CSF1R) Activates AKT/mTOR Signaling and Promotes T-Cell Lymphoma Viability. Clinical cancer research : an official journal of the American Association for Cancer Research 54 31636099
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
2022 Silence of a dependence receptor CSF1R in colorectal cancer cells activates tumor-associated macrophages. Journal for immunotherapy of cancer 52 36600555
1988 Colony-stimulating factor-1 receptor (c-fms). Journal of cellular biochemistry 52 2852667
2021 Clinical Development of Colony-Stimulating Factor 1 Receptor (CSF1R) Inhibitors. Journal of immunotherapy and precision oncology 51 35663534
2021 Targeting CSF1R Alone or in Combination with PD1 in Experimental Glioma. Cancers 50 34063518
2020 Attenuated CSF-1R signalling drives cerebrovascular pathology. EMBO molecular medicine 47 33350588
2008 An anti-c-Fms antibody inhibits orthodontic tooth movement. Journal of dental research 47 18362327
1995 Monocyte infiltration and c-fms expression in hearts of spontaneously hypertensive rats. Hypertension (Dallas, Tex. : 1979) 47 7843744
2021 Treatment of CSF1R-Related Leukoencephalopathy: Breaking New Ground. Movement disorders : official journal of the Movement Disorder Society 45 34329526
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
2024 Insights into CSF-1R Expression in the Tumor Microenvironment. Biomedicines 39 39457693
2011 Defining the anatomical localisation of subsets of the murine mononuclear phagocyte system using integrin alpha X (Itgax, CD11c) and colony stimulating factor 1 receptor (Csf1r, CD115) expression fails to discriminate dendritic cells from macrophages. Immunobiology 39 21885153
2023 The RNA m6A demethylase ALKBH5 drives emergency granulopoiesis and neutrophil mobilization by upregulating G-CSFR expression. Cellular & molecular immunology 38 38114747
2020 Small-molecule CSF1R kinase inhibitors; review of patents 2015-present. Expert opinion on therapeutic patents 37 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
2020 G-CSF and G-CSFR Induce a Pro-Tumorigenic Macrophage Phenotype to Promote Colon and Pancreas Tumor Growth. Cancers 32 33036138
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
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 G-CSFR antagonism reduces neutrophilic inflammation during pneumococcal and influenza respiratory infections without compromising clearance. Scientific reports 30 31776393
2019 Clinicopathologic characterization and abnormal autophagy of CSF1R-related leukoencephalopathy. Translational neurodegeneration 30 31827782
2009 Induction of endometrial epithelial cell invasion and c-fms expression by transforming growth factor beta. Molecular human reproduction 29 19505996
2024 CSF-1R in Cancer: More than a Myeloid Cell Receptor. Cancers 28 38254773
2018 A dual-specific macrophage colony-stimulating factor antagonist of c-FMS and αvβ3 integrin for osteoporosis therapy. PLoS biology 27 30142160
2020 CSF1R Is Required for Differentiation and Migration of Langerhans Cells and Langerhans Cell Histiocytosis. Cancer immunology research 26 32238382
2022 A kinase-dead Csf1r mutation associated with adult-onset leukoencephalopathy has a dominant inhibitory impact on CSF1R signalling. Development (Cambridge, England) 25 35333324
2011 c-FMS inhibitors: a patent review. Expert opinion on therapeutic patents 25 21204725
2011 The Src-like adaptor protein regulates GM-CSFR signaling and monocytic dendritic cell maturation. Journal of immunology (Baltimore, Md. : 1950) 25 21220694
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
1994 The function of c-fms in hairy-cell leukemia: macrophage colony-stimulating factor stimulates hairy-cell movement. Blood 24 8118039
1988 The colony-stimulating factor 1 (CSF-1) receptor (c-fms proto-oncogene product) and its ligand. Journal of cell science. Supplement 24 2978516
2020 Inhibition of CSF1R and AKT by (±)-kusunokinin hinders breast cancer cell proliferation. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 23 32535390
2024 Deplete and repeat: microglial CSF1R inhibition and traumatic brain injury. Frontiers in cellular neuroscience 22 38450286
2024 The Phenotypic and Genotypic Spectrum of CSF1R-Related Disorder in China. Movement disorders : official journal of the Movement Disorder Society 21 38465843
2024 CSF1R-Related Disorder: Prevalence of CSF1R Variants and Their Clinical Significance in the UK Population. Neurology. Genetics 21 39040919
2020 SWATH-Proteomics of Ibrutinib's Action in Myeloid Leukemia Initiating Mutated G-CSFR Signaling. Proteomics. Clinical applications 20 32319217
2021 G-CSFR antagonism reduces mucosal injury and airways fibrosis in a virus-dependent model of severe asthma. British journal of pharmacology 19 33609280
2019 Csf1r or Mer inhibition delays liver regeneration via suppression of Kupffer cells. PloS one 19 31042769
2012 Defective G-CSFR signaling pathways in congenital neutropenia. Hematology/oncology clinics of North America 19 23351989
2007 STAP-2 regulates c-Fms/M-CSF receptor signaling in murine macrophage Raw 264.7 cells. Biochemical and biophysical research communications 19 17512498
1987 Detection of c-fms and CSF-1 RNA by in situ hybridization. Leukemia 19 2444833
2007 Novel effect of estrogen on RANK and c-fms expression in RAW 264.7 cells. International journal of molecular medicine 18 17549395
2022 CSF1/CSF1R signaling mediates malignant pleural effusion formation. JCI insight 17 35315360
2013 Cloning and expression analysis of grouper (Epinephelus coioides) M-CSFR gene post Cryptocaryon irritans infection and distribution of M-CSFR(+) cells. Fish & shellfish immunology 17 23643873
2013 An anti-c-Fms antibody inhibits osteoclastogenesis in a mouse periodontitis model. Oral diseases 17 23651419
2012 c-Fms signaling mediates neurofibromatosis Type-1 osteoclast gain-in-functions. PloS one 17 23144792
2025 CSF1R+ myeloid-monocytic cells drive CAR-T cell resistance in aggressive B cell lymphoma. Cancer cell 16 40513575
2022 M-CSFR/CSF1R signaling regulates myeloid fates in zebrafish via distinct action of its receptors and ligands. Blood advances 16 34979548
2021 The CSF1R-Microglia Axis Has Protective Host-Specific Roles During Neurotropic Picornavirus Infection. Frontiers in immunology 16 34566948
2016 iRhom2 regulates CSF1R cell surface expression and non-steady state myelopoiesis in mice. European journal of immunology 16 27601030
2016 Resident corneal c-fms(+) macrophages and dendritic cells mediate early cellular infiltration in adenovirus keratitis. Experimental eye research 15 27185163
2003 C-fms expression correlates with monocytic differentiation in PML-RAR alpha+ acute promyelocytic leukemia. Leukemia 15 12529666
2017 Design, synthesis and optimization of bis-amide derivatives as CSF1R inhibitors. Bioorganic & medicinal chemistry letters 14 28377059
2023 Challenges and prospects of CSF1R targeting for advanced malignancies. American journal of cancer research 13 37560003

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