Colony-stimulating factor receptor

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Contents

Function

Colony-stimulating factor receptor (CSFR) are binding the Colony-stimulating factors and thus mediating the lineage-specific growth of cells of the mononuclear phagocytes series as bone marrow-derived precursors of monocytes and macrophages[1].

  • Macrophage colony stimulating factor receptor (M-CSFR) cause the hematopoietic stem cells to differentiate into macrophages or related cell types.
  • Granulocyte-macrophage colony stimulating factor receptor (GM-CSFR) regulates the production and activation of of hemopoietic cells as monocytes, macrophages and granulocytesparticipates in the development, survival and activation of neutrophilic granulocytes and controls dendritic cells and T-cell function[2].
  • Granulocyte colony stimulating factor receptor (G-CSFR) participates in the development, survival and activation of neutrophilic granulocytes and in the development of other myeloid lineages[3].

See also

Disease

Mutations in G-CSFR were found in patients with severe congenital neutropenia[4] and are associated with the progression of acute myeloid leukemia[5].

Relevance

An increase in the presence of M-CSFR is observed in ovarian tumor cells[6].

Structural highlights

The kinase domain of M-CSFR interacts with a drug-designed inhibitor via the conserved kinase DFG motif (colored in salmon) and its gatekeeper threonine residue (colored in magenta)[7].

3D structures of colony-stimulating factor receptor

Colony-stimulating factor receptor 3D structures


Human macrophage colony stimulating factor receptor kinase domain complex with inhibitor (PDB code 4hw7)

Drag the structure with the mouse to rotate

References

  1. Sherr CJ, Roussel MF, Rettenmier CW. Colony-stimulating factor-1 receptor (c-fms). J Cell Biochem. 1988 Nov;38(3):179-87. doi: 10.1002/jcb.240380305. PMID:2852667 doi:http://dx.doi.org/10.1002/jcb.240380305
  2. Hercus TR, Thomas D, Guthridge MA, Ekert PG, King-Scott J, Parker MW, Lopez AF. The granulocyte-macrophage colony-stimulating factor receptor: linking its structure to cell signaling and its role in disease. Blood. 2009 Aug 13;114(7):1289-98. doi: 10.1182/blood-2008-12-164004. Epub 2009, May 12. PMID:19436055 doi:http://dx.doi.org/10.1182/blood-2008-12-164004
  3. Liongue C, Wright C, Russell AP, Ward AC. Granulocyte colony-stimulating factor receptor: stimulating granulopoiesis and much more. Int J Biochem Cell Biol. 2009 Dec;41(12):2372-5. doi:, 10.1016/j.biocel.2009.08.011. Epub 2009 Aug 21. PMID:19699815 doi:http://dx.doi.org/10.1016/j.biocel.2009.08.011
  4. Dong F, Dale DC, Bonilla MA, Freedman M, Fasth A, Neijens HJ, Palmblad J, Briars GL, Carlsson G, Veerman AJ, Welte K, Lowenberg B, Touw IP. Mutations in the granulocyte colony-stimulating factor receptor gene in patients with severe congenital neutropenia. Leukemia. 1997 Jan;11(1):120-5. PMID:9001427
  5. Dong F, Brynes RK, Tidow N, Welte K, Lowenberg B, Touw IP. Mutations in the gene for the granulocyte colony-stimulating-factor receptor in patients with acute myeloid leukemia preceded by severe congenital neutropenia. N Engl J Med. 1995 Aug 24;333(8):487-93. doi: 10.1056/NEJM199508243330804. PMID:7542747 doi:http://dx.doi.org/10.1056/NEJM199508243330804
  6. Toy EP, Chambers JT, Kacinski BM, Flick MB, Chambers SK. The activated macrophage colony-stimulating factor (CSF-1) receptor as a predictor of poor outcome in advanced epithelial ovarian carcinoma. Gynecol Oncol. 2001 Feb;80(2):194-200. doi: 10.1006/gyno.2000.6070. PMID:11161859 doi:http://dx.doi.org/10.1006/gyno.2000.6070
  7. Zhang C, Ibrahim PN, Zhang J, Burton EA, Habets G, Zhang Y, Powell B, West BL, Matusow B, Tsang G, Shellooe R, Carias H, Nguyen H, Marimuthu A, Zhang KY, Oh A, Bremer R, Hurt CR, Artis DR, Wu G, Nespi M, Spevak W, Lin P, Nolop K, Hirth P, Tesch GH, Bollag G. Design and pharmacology of a highly specific dual FMS and KIT kinase inhibitor. Proc Natl Acad Sci U S A. 2013 Mar 14. PMID:23493555 doi:http://dx.doi.org/10.1073/pnas.1219457110

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Michal Harel, Alexander Berchansky

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