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Gene Review

Csf1r  -  colony stimulating factor 1 receptor

Mus musculus

Synonyms: AI323359, CD115, CSF-1 receptor, CSF-1-R, CSF-1R, ...
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Disease relevance of Csf1r

  • RESULTS AND CONCLUSIONS: Frequent spontaneous fractures and decreased strength parameters (ultimate load, yield load, and stiffness) in a three-point bending assay showed the biomechanical weakness of long bones in Csf1r(-/-) mice [1].
  • 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 [2].
  • This apparent role for CSF-1/CSF-1R in normal mammary gland development is very intriguing because this receptor/ligand pair has also been found to be important in the biology of breast cancer, where they regulate tumor cell invasion by a urokinase-dependent mechanism [3].
  • A c-fms tyrosine kinase inhibitor, Ki20227, suppresses osteoclast differentiation and osteolytic bone destruction in a bone metastasis model [4].
  • In this study, we investigated whether an inhibitor of M-CSF receptor (c-Fms) suppresses osteoclast-dependent osteolysis in bone metastatic lesions [4].

Psychiatry related information on Csf1r


High impact information on Csf1r

  • Factor switching experiments have shown that both multi-CSF and GM-CSF act dominantly and in a factor concentration dependent manner to suppress c-fms expression [6].
  • Although expression of the c-fms product (CSF-1 receptor) is normally restricted to cells of the mononuclear phagocyte series, the v-fms-coded glycoprotein can contribute to proliferative abnormalities of multiple hematopoietic lineages [7].
  • This putative product of the murine c-fms gene exhibited an associated tyrosine kinase activity in immune complexes, specifically bound murine CSF-1, and, in the presence of the growth factor, was phosphorylated on tyrosine in membrane preparations [8].
  • Rabbit antisera to a recombinant v-fms-coded polypeptide precipitated the feline c-fms product and specifically cross-reacted with a 165 kd glycoprotein from mouse macrophages [8].
  • The feline c-fms proto-oncogene product is a 170 kd glycoprotein with associated tyrosine kinase activity [8].

Chemical compound and disease context of Csf1r


Biological context of Csf1r

  • We observed that, concomitant with Csf1r downregulation, 32D/WT1 cells lost the ability to undergo myeloid differentiation in response to the granulocyte macrophage colony-stimulating factor (GM-CSF) [12].
  • Csf1r(-/-) mice therefore represent an ideal model system in which to investigate regulation by the osteoclast of osteoblast-mediated bone formation during development [1].
  • Excision of this floxed sequence results in a null allele that in the homozygous state gives a phenotype indistinguishable of the complete Csf1r null mutant mouse [13].
  • The interaction of cytoplasmic signalling molecules with CSF-1R is mediated in part by sequence motifs flanking sites of receptor tyrosine phosphorylation [14].
  • These results provide genetic evidence that in NIH-3T3 cells, ras p21 is involved in signal transduction mediated by CSF-1R [15].

Anatomical context of Csf1r

  • Consequently, the primary defect in osteopetrotic Csf1r(-/-) mice is severe osteoclast deficiency [1].
  • While individual osteoblasts in Csf1r(-/-) mice have preserved their typical ultrastructure and matrix depositing activity, the layered organization of osteoblasts on the bone-forming surface and the direction of their matrix deposition toward the bone surface have been lost, resulting in their abnormal entrapment by matrix [1].
  • Deletion of the entire kinase insert domain completely abrogates signal transduction by the CSF-1 receptor expressed in Rat-2 fibroblasts [16].
  • These results strongly suggest that the interaction of signals by means of VEGFR-1 and the CSF-1 receptor plays a predominant role not only in osteoclastogenesis but also in the maintenance of bone marrow functions [17].
  • The high level of CSF-1R mRNA expression by trophoblast giant cells was independent of their location around the conceptus [18].

Associations of Csf1r with chemical compounds


Physical interactions of Csf1r

  • Specific structural proteins associated with the separate CSF-1R multimeric complexes upon CSF-1 stimulation and the presence of the distinct pools of the CSF-1R were dependent on the integrity of the microtubular network [24].
  • So far among these candidate proteins, dynein, claudin and silencer of death domains co-immunoprecipitated with the CSF-1R, suggesting association [25].
  • In contrast, the CSF1R/IRA960 co-precipitates poorly with IRS-2 [26].
  • Transcription factor complex formation and chromatin fine structure alterations at the murine c-fms (CSF-1 receptor) locus during maturation of myeloid precursor cells [27].

Enzymatic interactions of Csf1r


Regulatory relationships of Csf1r


Other interactions of Csf1r


Analytical, diagnostic and therapeutic context of Csf1r


  1. Osteoclast deficiency results in disorganized matrix, reduced mineralization, and abnormal osteoblast behavior in developing bone. Dai, X.M., Zong, X.H., Akhter, M.P., Stanley, E.R. J. Bone Miner. Res. (2004) [Pubmed]
  2. 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. Dai, X.M., Ryan, G.R., Hapel, A.J., Dominguez, M.G., Russell, R.G., Kapp, S., Sylvestre, V., Stanley, E.R. Blood (2002) [Pubmed]
  3. The role of CSF-1 in normal and neoplastic breast physiology. Sapi, E., Kacinski, B.M. Proc. Soc. Exp. Biol. Med. (1999) [Pubmed]
  4. A c-fms tyrosine kinase inhibitor, Ki20227, suppresses osteoclast differentiation and osteolytic bone destruction in a bone metastasis model. Ohno, H., Kubo, K., Murooka, H., Kobayashi, Y., Nishitoba, T., Shibuya, M., Yoneda, T., Isoe, T. Mol. Cancer Ther. (2006) [Pubmed]
  5. Accelerated phagocytosis of amyloid-beta by mouse and human microglia overexpressing the macrophage colony-stimulating factor receptor. Mitrasinovic, O.M., Murphy, G.M. J. Biol. Chem. (2002) [Pubmed]
  6. Expression of the M-CSF receptor is controlled posttranscriptionally by the dominant actions of GM-CSF or multi-CSF. Gliniak, B.C., Rohrschneider, L.R. Cell (1990) [Pubmed]
  7. Multilineage hematopoietic disorders induced by transplantation of bone marrow cells expressing the v-fms oncogene. Heard, J.M., Roussel, M.F., Rettenmier, C.W., Sherr, C.J. Cell (1987) [Pubmed]
  8. The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Sherr, C.J., Rettenmier, C.W., Sacca, R., Roussel, M.F., Look, A.T., Stanley, E.R. Cell (1985) [Pubmed]
  9. SU11248 inhibits tumor growth and CSF-1R-dependent osteolysis in an experimental breast cancer bone metastasis model. Murray, L.J., Abrams, T.J., Long, K.R., Ngai, T.J., Olson, L.M., Hong, W., Keast, P.K., Brassard, J.A., O'Farrell, A.M., Cherrington, J.M., Pryer, N.K. Clin. Exp. Metastasis (2003) [Pubmed]
  10. Nitric oxide induction in murine macrophages and spleen cells by whole-cell Bordetella pertussis vaccine. Xing, D.K., Canthaboo, C., Corbel, M.J. Vaccine (1998) [Pubmed]
  11. Correlation of tumor phenotype with c-fms proto-oncogene expression in an in vivo intraperitoneal model for experimental human breast cancer metastasis. Toy, E.P., Bonafé, N., Savlu, A., Zeiss, C., Zheng, W., Flick, M., Chambers, S.K. Clin. Exp. Metastasis (2005) [Pubmed]
  12. Myeloid maturation block by AML1-MTG16 is associated with Csf1r epigenetic downregulation. Rossetti, S., Van Unen, L., Touw, I.P., Hoogeveen, A.T., Sacchi, N. Oncogene (2005) [Pubmed]
  13. Conditional deletion of the colony stimulating factor-1 receptor (c-fms proto-oncogene) in mice. Li, J., Chen, K., Zhu, L., Pollard, J.W. Genesis (2006) [Pubmed]
  14. Myc rescue of a mutant CSF-1 receptor impaired in mitogenic signalling. Roussel, M.F., Cleveland, J.L., Shurtleff, S.A., Sherr, C.J. Nature (1991) [Pubmed]
  15. The carboxy-terminal catalytic domain of the GTPase-activating protein inhibits nuclear signal transduction and morphological transformation mediated by the CSF-1 receptor. Bortner, D.M., Ulivi, M., Roussel, M.F., Ostrowski, M.C. Genes Dev. (1991) [Pubmed]
  16. Mutation of Tyr697, a GRB2-binding site, and Tyr721, a PI 3-kinase binding site, abrogates signal transduction by the murine CSF-1 receptor expressed in Rat-2 fibroblasts. van der Geer, P., Hunter, T. EMBO J. (1993) [Pubmed]
  17. VEGF receptor 1 signaling is essential for osteoclast development and bone marrow formation in colony-stimulating factor 1-deficient mice. Niida, S., Kondo, T., Hiratsuka, S., Hayashi, S., Amizuka, N., Noda, T., Ikeda, K., Shibuya, M. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  18. Temporal expression and location of colony-stimulating factor 1 (CSF-1) and its receptor in the female reproductive tract are consistent with CSF-1-regulated placental development. Arceci, R.J., Shanahan, F., Stanley, E.R., Pollard, J.W. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  19. Tyrosine 706 and 807 phosphorylation site mutants in the murine colony-stimulating factor-1 receptor are unaffected in their ability to bind or phosphorylate phosphatidylinositol-3 kinase but show differential defects in their ability to induce early response gene transcription. van der Geer, P., Hunter, T. Mol. Cell. Biol. (1991) [Pubmed]
  20. 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. Rossner, M.T., McArthur, G.A., Allen, J.D., Metcalf, D. Cell Growth Differ. (1994) [Pubmed]
  21. Chemical-induced hippocampal neurodegeneration and elevations in TNFalpha, TNFbeta, IL-1alpha, IP-10, and MCP-1 mRNA in osteopetrotic (op/op) mice. Bruccoleri, A., Harry, G.J. J. Neurosci. Res. (2000) [Pubmed]
  22. c-Fms and the alphavbeta3 integrin collaborate during osteoclast differentiation. Faccio, R., Takeshita, S., Zallone, A., Ross, F.P., Teitelbaum, S.L. J. Clin. Invest. (2003) [Pubmed]
  23. A point mutation at tyrosine-809 in the human colony-stimulating factor 1 receptor impairs mitogenesis without abrogating tyrosine kinase activity, association with phosphatidylinositol 3-kinase, or induction of c-fos and junB genes. Roussel, M.F., Shurtleff, S.A., Downing, J.R., Sherr, C.J. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  24. Separation and characterization of the activated pool of colony-stimulating factor 1 receptor forming distinct multimeric complexes with signalling molecules in macrophages. Kanagasundaram, V., Jaworowski, A., Byrne, R., Hamilton, J.A. Mol. Cell. Biol. (1999) [Pubmed]
  25. A proteomics strategy for the enrichment of receptor-associated complexes. Cross, M., Nguyen, T., Bogdanoska, V., Reynolds, E., Hamilton, J.A. Proteomics (2005) [Pubmed]
  26. Mutation of tyrosine 960 within the insulin receptor juxtamembrane domain impairs glucose transport but does not inhibit ligand-mediated phosphorylation of insulin receptor substrate-2 in 3T3-L1 adipocytes. Chaika, O.V., Chaika, N., Volle, D.J., Hayashi, H., Ebina, Y., Wang, L.M., Pierce, J.H., Lewis, R.E. J. Biol. Chem. (1999) [Pubmed]
  27. Transcription factor complex formation and chromatin fine structure alterations at the murine c-fms (CSF-1 receptor) locus during maturation of myeloid precursor cells. Tagoh, H., Himes, R., Clarke, D., Leenen, P.J., Riggs, A.D., Hume, D., Bonifer, C. Genes Dev. (2002) [Pubmed]
  28. A novel 110 kDa form of myosin XVIIIA (MysPDZ) is tyrosine-phosphorylated after colony-stimulating factor-1 receptor signalling. Cross, M., Csar, X.F., Wilson, N.J., Manes, G., Addona, T.A., Marks, D.C., Whitty, G.A., Ashman, K., Hamilton, J.A. Biochem. J. (2004) [Pubmed]
  29. Tyr721 regulates specific binding of the CSF-1 receptor kinase insert to PI 3'-kinase SH2 domains: a model for SH2-mediated receptor-target interactions. Reedijk, M., Liu, X., van der Geer, P., Letwin, K., Waterfield, M.D., Hunter, T., Pawson, T. EMBO J. (1992) [Pubmed]
  30. Macrophage colony-stimulating factor-induced tyrosine phosphorylation of c-fms proteins expressed in FDC-P1 and BALB/c 3T3 cells. Tapley, P., Kazlauskas, A., Cooper, J.A., Rohrschneider, L.R. Mol. Cell. Biol. (1990) [Pubmed]
  31. The PCH family member MAYP/PSTPIP2 directly regulates F-actin bundling and enhances filopodia formation and motility in macrophages. Chitu, V., Pixley, F.J., Macaluso, F., Larson, D.R., Condeelis, J., Yeung, Y.G., Stanley, E.R. Mol. Biol. Cell (2005) [Pubmed]
  32. A GM-colony-stimulating factor (CSF) activated ribonuclease system transregulates M-CSF receptor expression in the murine FDC-P1/MAC myeloid cell line. Gliniak, B.C., Park, L.S., Rohrschneider, L.R. Mol. Biol. Cell (1992) [Pubmed]
  33. Colony-stimulating factor-1 receptor utilizes multiple signaling pathways to induce cyclin D2 expression. Dey, A., She, H., Kim, L., Boruch, A., Guris, D.L., Carlberg, K., Sebti, S.M., Woodley, D.T., Imamoto, A., Li, W. Mol. Biol. Cell (2000) [Pubmed]
  34. CSF-1 stimulated multiubiquitination of the CSF-1 receptor and of Cbl follows their tyrosine phosphorylation and association with other signaling proteins. Wang, Y., Yeung, Y.G., Stanley, E.R. J. Cell. Biochem. (1999) [Pubmed]
  35. Accumulation of c-Cbl and rapid termination of colony-stimulating factor 1 receptor signaling in interferon consensus sequence binding protein-deficient bone marrow-derived macrophages. Kallies, A., Rosenbauer, F., Scheller, M., Knobeloch, K.P., Horak, I. Blood (2002) [Pubmed]
  36. Regulation of colony-stimulating factor 1 receptor signaling by the SH2 domain-containing tyrosine phosphatase SHPTP1. Chen, H.E., Chang, S., Trub, T., Neel, B.G. Mol. Cell. Biol. (1996) [Pubmed]
  37. Expression pattern and neurotrophic role of the c-fms proto-oncogene M-CSF receptor in rodent Purkinje cells. Murase, S., Hayashi, Y. J. Neurosci. (1998) [Pubmed]
  38. Increased circulating colony-stimulating factor-1 (CSF-1) in SJL/J mice with radiation-induced acute myeloid leukemia (AML) is associated with autocrine regulation of AML cells by CSF-1. Haran-Ghera, N., Krautghamer, R., Lapidot, T., Peled, A., Dominguez, M.G., Stanley, E.R. Blood (1997) [Pubmed]
  39. Production of colony-stimulating factor-1 (CSF-1) by mouse astroglia in vitro. Hao, C., Guilbert, L.J., Fedoroff, S. J. Neurosci. Res. (1990) [Pubmed]
  40. Targeted expression of csCSF-1 in op/op mice ameliorates tooth defects. Werner, S.A., Gluhak-Heinrich, J., Woodruff, K., Wittrant, Y., Cardenas, L., Roudier, M., Macdougall, M. Arch. Oral Biol. (2007) [Pubmed]
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