macrophage colony stimulating factor receptor


Summary: A receptor for MACROPHAGE COLONY-STIMULATING FACTOR encoded by the c-fms proto-oncogene (GENES, FMS). It contains an intrinsic protein-tyrosine kinase activity. When activated the receptor undergoes autophosphorylation, phosphorylation of down-stream signaling molecules and rapid down-regulation.

Top Publications

  1. Ikeda O, Sekine Y, Kakisaka M, Tsuji S, Muromoto R, Ohbayashi N, et al. STAP-2 regulates c-Fms/M-CSF receptor signaling in murine macrophage Raw 264.7 cells. Biochem Biophys Res Commun. 2007;358:931-7 pubmed
    ..Taken together, our findings demonstrate that STAP-2 directly binds to c-Fms and interferes with the PI3K signaling, which leads to macrophage motility, in Raw 264.7 cells. ..
  2. Conway J, Pink H, Bergquist M, Han B, Depee S, Tadepalli S, et al. Effects of the cFMS kinase inhibitor 5-(3-methoxy-4-((4-methoxybenzyl)oxy)benzyl)pyrimidine-2,4-diamine (GW2580) in normal and arthritic rats. J Pharmacol Exp Ther. 2008;326:41-50 pubmed publisher
    ..In conclusion, GW2580 was effective in preserving joint integrity in the adjuvant arthritis model while showing minimal effects in normal rats...
  3. Kitaura H, Zhou P, Kim H, Novack D, Ross F, Teitelbaum S. M-CSF mediates TNF-induced inflammatory osteolysis. J Clin Invest. 2005;115:3418-27 pubmed
    ..M-CSF and its receptor, c-Fms, therefore present as candidate therapeutic targets in states of inflammatory bone erosion. ..
  4. Tanaka S, Takahashi N, Udagawa N, Tamura T, Akatsu T, Stanley E, et al. Macrophage colony-stimulating factor is indispensable for both proliferation and differentiation of osteoclast progenitors. J Clin Invest. 1993;91:257-63 pubmed
    ..These results clearly indicate that M-CSF is indispensable for both proliferation of osteoclast progenitors and their differentiation into mature osteoclasts. ..
  5. Felix R, Cecchini M, Fleisch H. Macrophage colony stimulating factor restores in vivo bone resorption in the op/op osteopetrotic mouse. Endocrinology. 1990;127:2592-4 pubmed
  6. Kingston D, Schmid M, Onai N, Obata Onai A, Baumjohann D, Manz M. The concerted action of GM-CSF and Flt3-ligand on in vivo dendritic cell homeostasis. Blood. 2009;114:835-43 pubmed publisher
    ..These data thus show the concerted action of GM-CSF and Flt3-ligand on DC homeostasis in vivo. ..
  7. Fuhrman B, Partoush A, Volkova N, Aviram M. Ox-LDL induces monocyte-to-macrophage differentiation in vivo: Possible role for the macrophage colony stimulating factor receptor (M-CSF-R). Atherosclerosis. 2008;196:598-607 pubmed
    ..We thus conclude that Ox-LDL induces monocyte differentiation to macrophages in vivo and this phenomenon involves activation of the M-CSF-receptor. ..
  8. Ohno H, Kubo K, Murooka H, Kobayashi Y, Nishitoba T, Shibuya M, et al. A c-fms tyrosine kinase inhibitor, Ki20227, suppresses osteoclast differentiation and osteolytic bone destruction in a bone metastasis model. Mol Cancer Ther. 2006;5:2634-43 pubmed
    ..Therefore, Ki20227 may be a useful therapeutic agent for osteolytic disease associated with bone metastasis and other bone diseases. ..
  9. Paniagua R, Sharpe O, Ho P, Chan S, Chang A, Higgins J, et al. Selective tyrosine kinase inhibition by imatinib mesylate for the treatment of autoimmune arthritis. J Clin Invest. 2006;116:2633-42 pubmed
    ..Imatinib-mediated inhibition of a spectrum of signal transduction pathways and the downstream pathogenic cellular responses may provide a powerful approach to treat RA and other inflammatory diseases. ..

More Information


  1. Irvine K, Burns C, Wilks A, Su S, Hume D, Sweet M. A CSF-1 receptor kinase inhibitor targets effector functions and inhibits pro-inflammatory cytokine production from murine macrophage populations. FASEB J. 2006;20:1921-3 pubmed
    ..CSF-1R inhibitors such as CYC10268 provide a powerful tool to dissect the role of the CSF-1/CSF-1R signaling system in a range of biological systems and have potential for a number of therapeutic applications. ..
  2. MacDonald K, Rowe V, Bofinger H, Thomas R, Sasmono T, Hume D, et al. The colony-stimulating factor 1 receptor is expressed on dendritic cells during differentiation and regulates their expansion. J Immunol. 2005;175:1399-405 pubmed
    ..These data provide additional evidence that the majority of tissue DC is of myeloid origin during steady state and supports a close relationship between DC and macrophage biology in vivo. ..
  3. Pixley F, Stanley E. CSF-1 regulation of the wandering macrophage: complexity in action. Trends Cell Biol. 2004;14:628-38 pubmed
    ..Because CSF-1 regulates the survival, proliferation and chemotaxis of macrophages and supports their activation, this factor is involved in the pathogenesis of several diseases. ..
  4. Burnett S, Kershen E, Zhang J, Zeng L, Straley S, Kaplan A, et al. Conditional macrophage ablation in transgenic mice expressing a Fas-based suicide gene. J Leukoc Biol. 2004;75:612-23 pubmed
    ..This new, transgenic line will be useful in investigating the role of macrophages and DC. ..
  5. Ide H, Seligson D, Memarzadeh S, Xin L, Horvath S, Dubey P, et al. Expression of colony-stimulating factor 1 receptor during prostate development and prostate cancer progression. Proc Natl Acad Sci U S A. 2002;99:14404-9 pubmed
    ..These observations correlate CSF-1R expression with changes in the growth and development of the normal and neoplastic prostate. ..
  6. Dai X, Ryan G, Hapel A, Dominguez M, Russell R, Kapp S, et al. Targeted disruption of the mouse colony-stimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects. Blood. 2002;99:111-20 pubmed
    ..The results indicate that all of the effects of CSF-1 are mediated via the CSF-1R, but that subtle effects of the CSF-1R could result from its CSF-1-independent activation. ..
  7. Marks D, Csar X, Wilson N, Novak U, Ward A, Kanagasundarum V, et al. Expression of a Y559F mutant CSF-1 receptor in M1 myeloid cells: a role for Src kinases in CSF-1 receptor-mediated differentiation. Mol Cell Biol Res Commun. 1999;1:144-52 pubmed
    ..These data suggest that the reduced Src binding observed in the M1/Y559F cells may contribute to their reduced ability to differentiate. ..
  8. Stanley E, Berg K, Einstein D, Lee P, Pixley F, Wang Y, et al. Biology and action of colony--stimulating factor-1. Mol Reprod Dev. 1997;46:4-10 pubmed
    ..Studies on several of these proteins, including protein tyrosine phosphates 1C, the c-cbl proto-oncogene product, and protein tyrosine phosphatase-phi are discussed. ..
  9. Onai N, Obata Onai A, Schmid M, Ohteki T, Jarrossay D, Manz M. Identification of clonogenic common Flt3+M-CSFR+ plasmacytoid and conventional dendritic cell progenitors in mouse bone marrow. Nat Immunol. 2007;8:1207-16 pubmed
    ..These clonogenic common DC progenitors thus define a cytokine-regulated DC developmental pathway that ensures the supply of various DC populations. ..
  10. Auffray C, Sieweke M, Geissmann F. Blood monocytes: development, heterogeneity, and relationship with dendritic cells. Annu Rev Immunol. 2009;27:669-92 pubmed publisher
    ..Functional characterization of monocytes is in progress in humans and rodents and will provide a better understanding of the pathophysiology of inflammation. ..
  11. Auffray C, Fogg D, Narni Mancinelli E, Senechal B, Trouillet C, Saederup N, et al. CX3CR1+ CD115+ CD135+ common macrophage/DC precursors and the role of CX3CR1 in their response to inflammation. J Exp Med. 2009;206:595-606 pubmed publisher
    ..CX(3)CR1 deficiency selectively impairs the recruitment of blood Gr1(+) monocytes in the spleen after transfer and during acute Listeria monocytogenes infection but does not affect the development of monocytes, cDCs, and PDCs. ..
  12. Sakai H, Chen Y, Itokawa T, Yu K, Zhu M, Insogna K. Activated c-Fms recruits Vav and Rac during CSF-1-induced cytoskeletal remodeling and spreading in osteoclasts. Bone. 2006;39:1290-301 pubmed
    ..These data demonstrate that Vav and Rac lie downstream from activated PI3-K in CSF-1-treated osteoclasts and that Rac is required for CSF-1-induced cytoskeletal remodeling in these cells. ..
  13. Ginhoux F, Liu K, Helft J, Bogunovic M, Greter M, Hashimoto D, et al. The origin and development of nonlymphoid tissue CD103+ DCs. J Exp Med. 2009;206:3115-30 pubmed publisher
    ..Our results reveal that nonlymphoid tissue CD103(+) DCs and lymphoid organ CD8(+) DCs derive from the same precursor and follow a related differentiation program. ..
  14. Dewar A, Cambareri A, Zannettino A, Miller B, Doherty K, Hughes T, et al. Macrophage colony-stimulating factor receptor c-fms is a novel target of imatinib. Blood. 2005;105:3127-32 pubmed
    ..Imatinib should now be assessed for activity in diseases where c-fms activation is implicated, including breast and ovarian cancer and inflammatory conditions. ..
  15. Wang Z, Myles G, Brandt C, Lioubin M, Rohrschneider L. Identification of the ligand-binding regions in the macrophage colony-stimulating factor receptor extracellular domain. Mol Cell Biol. 1993;13:5348-59 pubmed
    ..These results suggest that the three N-terminal immunoglobulin-like domains constitute the high-affinity M-CSF binding region and that the fourth and fifth immunoglobulin-like domains may perform functions other than ligand binding. ..
  16. Aharinejad S, Paulus P, Sioud M, Hofmann M, Zins K, Schäfer R, et al. Colony-stimulating factor-1 blockade by antisense oligonucleotides and small interfering RNAs suppresses growth of human mammary tumor xenografts in mice. Cancer Res. 2004;64:5378-84 pubmed
    ..In addition, mouse survival significantly increased after CSF-1 blockade. These studies demonstrate that CSF-1 and CSF-1 receptor are potential therapeutic targets for the treatment of mammary cancer. ..
  17. Mitrasinovic O, Robinson C, Tenen D, Lee Y, Poon C, Murphy G. Biolistic expression of the macrophage colony stimulating factor receptor in organotypic cultures induces an inflammatory response. J Neurosci Res. 2004;77:420-9 pubmed
  18. Faccio R, Takeshita S, Zallone A, Ross F, Teitelbaum S. c-Fms and the alphavbeta3 integrin collaborate during osteoclast differentiation. J Clin Invest. 2003;111:749-58 pubmed
    ..Thus, while c-Fms and alpha(v)beta(3) collaborate in the osteoclastogenic process via shared activation of the ERK/c-Fos signaling pathway, the integrin is essential for matrix degradation. ..
  19. Jose M, Le Meur Y, Atkins R, Chadban S. Blockade of macrophage colony-stimulating factor reduces macrophage proliferation and accumulation in renal allograft rejection. Am J Transplant. 2003;3:294-300 pubmed
    ..This pathway plays a significant and specific role in the accumulation of macrophages within a rejecting renal allograft. ..
  20. Sasmono R, Oceandy D, Pollard J, Tong W, Pavli P, Wainwright B, et al. A macrophage colony-stimulating factor receptor-green fluorescent protein transgene is expressed throughout the mononuclear phagocyte system of the mouse. Blood. 2003;101:1155-63 pubmed
    ..We have therefore defined the elements required to generate myeloid- and trophoblast-specific transgenes as well as a model system for the study of mononuclear phagocyte development and function. ..
  21. Hamilton J. CSF-1 signal transduction. J Leukoc Biol. 1997;62:145-55 pubmed
    ..The relevance of any potentially important molecular signaling pathway activated by CSF-1 in cells in vitro will ultimately have to be related to the functions of monocytes/macrophages in vivo. ..
  22. Flick M, Sapi E, Kacinski B. Hormonal regulation of the c-fms proto-oncogene in breast cancer cells is mediated by a composite glucocorticoid response element. J Cell Biochem. 2002;85:10-23 pubmed
  23. Tagoh H, Himes R, Clarke D, Leenen P, Riggs A, Hume D, et al. Transcription factor complex formation and chromatin fine structure alterations at the murine c-fms (CSF-1 receptor) locus during maturation of myeloid precursor cells. Genes Dev. 2002;16:1721-37 pubmed
    Expression of the gene for the macrophage colony stimulating factor receptor (CSF-1R), c-fms, has been viewed as a hallmark of the commitment of multipotent precursor cells to macrophages...
  24. Wilhelmsen K, Burkhalter S, van der Geer P. C-Cbl binds the CSF-1 receptor at tyrosine 973, a novel phosphorylation site in the receptor's carboxy-terminus. Oncogene. 2002;21:1079-89 pubmed
    ..Our observations are consistent with a model in which receptor autophosphorylation at Tyr 973 creates a binding site for c-Cbl. Association of c-Cbl with the receptor leads to ubiquitination, followed by receptor degradation. ..
  25. Conway J, McDonald B, Parham J, Keith B, Rusnak D, Shaw E, et al. Inhibition of colony-stimulating-factor-1 signaling in vivo with the orally bioavailable cFMS kinase inhibitor GW2580. Proc Natl Acad Sci U S A. 2005;102:16078-83 pubmed
    ..The ability of GW2580 to chronically inhibit CSF-1 signaling through cFMS kinase in normal and tumor cells in vivo makes GW2580 a useful tool in assessing the role of cFMS kinase in normal and disease processes. ..
  26. Bogunovic M, Ginhoux F, Helft J, Shang L, Hashimoto D, Greter M, et al. Origin of the lamina propria dendritic cell network. Immunity. 2009;31:513-25 pubmed publisher
    ..Altogether, these results underline the diverse origin of the lamina propria DC network and identify mucosal DCs that arise from pre-DCs as key sentinels of the gut immune system. ..
  27. Paulus P, Stanley E, Schäfer R, Abraham D, Aharinejad S. Colony-stimulating factor-1 antibody reverses chemoresistance in human MCF-7 breast cancer xenografts. Cancer Res. 2006;66:4349-56 pubmed
    ..These studies support the paradigm of CSF-1 blockade in the treatment of solid tumors and show that anti-CSF-1 antibodies are potential therapeutic agents for the treatment of mammary cancer. ..
  28. Kacinski B, Scata K, Carter D, Yee L, Sapi E, King B, et al. FMS (CSF-1 receptor) and CSF-1 transcripts and protein are expressed by human breast carcinomas in vivo and in vitro. Oncogene. 1991;6:941-52 pubmed
    ..These results suggest that autocrine and paracrine interactions of the lymphohematopoietic cytokine CSF-1 and its receptor may participate in the biology of human mammary neoplasms. ..
  29. Chomarat P, Dantin C, Bennett L, Banchereau J, Palucka A. TNF skews monocyte differentiation from macrophages to dendritic cells. J Immunol. 2003;171:2262-9 pubmed
    ..Thus, TNF facilitates the induction of adaptive immunity by promoting DC differentiation not only from CD34+ progenitors but also from CD14+ blood precursors. ..
  30. Morimoto H, Takahashi M, Shiba Y, Izawa A, Ise H, Hongo M, et al. Bone marrow-derived CXCR4+ cells mobilized by macrophage colony-stimulating factor participate in the reduction of infarct area and improvement of cardiac remodeling after myocardial infarction in mice. Am J Pathol. 2007;171:755-66 pubmed
  31. Lichanska A, Browne C, Henkel G, Murphy K, Ostrowski M, McKercher S, et al. Differentiation of the mononuclear phagocyte system during mouse embryogenesis: the role of transcription factor PU.1. Blood. 1999;94:127-38 pubmed
    ..The results support previous evidence that yolk sac-derived fetal phagocytes are functionally distinct from those arising in the liver and develop via a different pathway. ..
  32. Yen A, Varvayanis S, Smith J, Lamkin T. Retinoic acid induces expression of SLP-76: expression with c-FMS enhances ERK activation and retinoic acid-induced differentiation/G0 arrest of HL-60 cells. Eur J Cell Biol. 2006;85:117-32 pubmed
    ..This is the first indication to our knowledge that RA induces the expression of an adapter molecule to facilitate induced differentiation via co-operation between c-FMS and SLP-76. ..
  33. Mouchiroud G, Bourette R, Blanchet J. Expression of functional human CSF-1 receptors on mouse bone marrow erythroid progenitor cells. C R Acad Sci III. 1993;316:1290-6 pubmed
  34. Cross M, Nguyen T, Bogdanoska V, Reynolds E, Hamilton J. A proteomics strategy for the enrichment of receptor-associated complexes. Proteomics. 2005;5:4754-63 pubmed
    ..This affinity matrix method, using an entire cytoplasmic region, may have relevance for other growth factor receptors. ..
  35. Chang Y, Albright S, Lee F. Cytokines in the central nervous system: expression of macrophage colony stimulating factor and its receptor during development. J Neuroimmunol. 1994;52:9-17 pubmed
  36. Ilaria R. Tyrosine kinases in AML: where do they fit in?. Leuk Res. 2004;28:217-8 pubmed
  37. Lucas T, Abraham D, Untergasser G, Zins K, Hofer E, Gunsilius E, et al. Adenoviral-mediated endothelial precursor cell delivery of soluble CD115 suppresses human prostate cancer xenograft growth in mice. Stem Cells. 2009;27:2342-52 pubmed publisher
    ..03), and suppresses the growth of xenografts (p < .03). These data show for the first time that targeting stromal cell processes with cellular therapy has the potential to retard prostate tumor growth. ..
  38. Dave R, Hume D, Elsegood C, Kellie S. CD148/DEP-1 association with areas of cytoskeletal organisation in macrophages. Exp Cell Res. 2009;315:1734-44 pubmed publisher
    ..There were no detectable effects on the CSF-1 receptor-akt signalling pathway. These results are consistent with the hypothesis that CD148 is a regulator of macrophage activity. ..
  39. Kim N, Choi B, Huang X, Snyder B, Bukhari S, Kong T, et al. Granulocyte-macrophage colony-stimulating factor promotes survival of dopaminergic neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced murine Parkinson's disease model. Eur J Neurosci. 2009;29:891-900 pubmed publisher
    ..Furthermore, administration of GM-CSF (50 microg/kg body weight/day) in vivo for 7 days protected dopaminergic neurons in the substantia nigra and improved locomotor behavior in a mouse MPTP model of PD. ..
  40. Nakajima K, Graeber M, Sonoda M, Tohyama Y, Kohsaka S, Kurihara T. In vitro proliferation of axotomized rat facial nucleus-derived activated microglia in an autocrine fashion. J Neurosci Res. 2006;84:348-59 pubmed
    ..In summary, the microglia isolated from the axFN were found to be proliferative in an autocrine fashion and to have some cellular properties in common with those observed in vivo. ..
  41. Hanington P, Wang T, Secombes C, Belosevic M. Growth factors of lower vertebrates: characterization of goldfish (Carassius auratus L.) macrophage colony-stimulating factor-1. J Biol Chem. 2007;282:31865-72 pubmed
    ..The ability of the soluble CSF-1R to inhibit CSF-1-induced proliferation represents a novel mechanism for the regulation of CSF-1 function. ..
  42. Cupp J, Miller M, Montgomery K, Nielsen T, O Connell J, Huntsman D, et al. Translocation and expression of CSF1 in pigmented villonodular synovitis, tenosynovial giant cell tumor, rheumatoid arthritis and other reactive synovitides. Am J Surg Pathol. 2007;31:970-6 pubmed
  43. Pajusola K, Aprelikova O, Armstrong E, Morris S, Alitalo K. Two human FLT4 receptor tyrosine kinase isoforms with distinct carboxy terminal tails are produced by alternative processing of primary transcripts. Oncogene. 1993;8:2931-7 pubmed
    ..The significance of the two forms may relate to the role of additional potential autophosphorylation sites in the FLT4 long form. ..
  44. Li Y, Chen B. Differential regulation of fyn-associated protein tyrosine kinase activity by macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). J Leukoc Biol. 1995;57:484-90 pubmed
    ..Collectively, our data suggest that the activation of fyn kinase is closely associated with the acquisition of adherent capacity in maturing macrophages. ..
  45. Huang B, Pan P, Li Q, Sato A, Levy D, Bromberg J, et al. Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host. Cancer Res. 2006;66:1123-31 pubmed
    ..Our data provide evidence that Gr-1(+)CD115(+) MSC can mediate the development of Treg in tumor-bearing mice and show a novel immune suppressive mechanism by which MSCs can suppress antitumor responses. ..
  46. Yoshimura A, Sanada M, Mashima R. [Receptor tyrosine kinases (c-kit, c-fmns, Flt-3, Tie2, etc.)]. Nihon Rinsho. 2005;63 Suppl 4:207-14 pubmed
  47. Mauro L, Olmsted E, Skrobacz B, Mourey R, Davis A, Dixon J. Identification of a hormonally regulated protein tyrosine phosphatase associated with bone and testicular differentiation. J Biol Chem. 1994;269:30659-67 pubmed
    ..OST-PTP may function in signaling pathways during bone remodeling, as well as serve a broader role in cell interactions associated with differentiation in bone and testis. ..
  48. Ohashi H, Maruyama K, Liu Y, Yoshimura A. Ligand-induced activation of chimeric receptors between the erythropoietin receptor and receptor tyrosine kinases. Proc Natl Acad Sci U S A. 1994;91:158-62 pubmed
    ..These data demonstrate the interchangeability of domains between two distinct receptor families and suggest that ligand-induced dimerization is a key step in activating the EPOR. ..
  49. Segawa M, Fukada S, Yamamoto Y, Yahagi H, Kanematsu M, Sato M, et al. Suppression of macrophage functions impairs skeletal muscle regeneration with severe fibrosis. Exp Cell Res. 2008;314:3232-44 pubmed publisher
    ..These results indicate that macrophages directly affect satellite cell proliferation and that a macrophage deficiency severely impairs skeletal muscle regeneration and causes fibrosis. ..
  50. Ciraci E, Barisani D, Parafioriti A, Formisano G, Arancia G, Bottazzo G, et al. CD34 human hematopoietic progenitor cell line, MUTZ-3, differentiates into functional osteoclasts. Exp Hematol. 2007;35:967-77 pubmed
    ..Importantly, the data indicate that the CD14(+)CD34(+)M-CSF-R(+)RANK(+) population represents an intermediate stage of differentiation from CD34 precursors and monocytes to osteoclast. ..
  51. Seeger F, Chen L, Spyridopoulos I, Altschmied J, Aicher A, Haendeler J. Downregulation of ETS rescues diabetes-induced reduction of endothelial progenitor cells. PLoS ONE. 2009;4:e4529 pubmed publisher
    ..These data demonstrate that diabetes leads to dysregulated activation of ETS, which blocks the functional activity of progenitor cells and their commitment towards the endothelial cell lineage. ..
  52. Rossner M, McArthur G, Allen J, Metcalf D. Fms-like tyrosine kinase 3 catalytic domain can transduce a proliferative signal in FDC-P1 cells that is qualitatively similar to the signal delivered by c-Fms. Cell Growth Differ. 1994;5:549-55 pubmed
    ..abstract truncated at 250 words) ..
  53. Edelson B, Kc W, Juang R, Kohyama M, Benoit L, Klekotka P, et al. Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8alpha+ conventional dendritic cells. J Exp Med. 2010;207:823-36 pubmed publisher
    ..These data provide evidence for a developmental relationship between lymphoid organ-resident CD8alpha+ cDCs and nonlymphoid CD103+ DCs. ..