Colony stimulating factor 1 receptor

Colony stimulating factor 1 receptor

Rendering based on PDB 2I0V.
Identifiers
Symbols CSF1R; C-FMS; CD115; CSFR; FIM2; FMS
External IDs OMIM164770 MGI1339758 HomoloGene3817 GeneCards: CSF1R Gene
EC number 2.7.10.1
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 1436 12978
Ensembl ENSG00000182578 ENSMUSG00000024621
UniProt P07333 Q0P635
RefSeq (mRNA) NM_005211 NM_001037859.2
RefSeq (protein) NP_005202 NP_001032948.2
Location (UCSC) Chr 5:
149.43 – 149.49 Mb
Chr 18:
61.27 – 61.29 Mb
PubMed search [1] [2]

Colony stimulating factor 1 receptor (CSF1R), also known as macrophage colony-stimulating factor receptor (M-CSFR), and CD115 (Cluster of Differentiation 115), is a cell-surface protein encoded, in humans, by the CSF1R gene.[1][2] It is a receptor for a cytokine called colony stimulating factor 1.

Contents

Genomics

The gene is located on long arm of chromosome 5 (5q32) on the Crick (minus) strand. It is 60.002 kilobases in length. The encoded protein has 972 amino acids and a predicted molecular weight of 107.984 kiloDaltons. The first intron of the CSFR1 gene contains a transcriptionally inactive ribosomal protein L7 processed pseudogene, oriented in the opposite direction to the CSFR1 gene.[1]

Function

The endcoded protein is a single pass type I membrane protein and acts as the receptor for colony stimulating factor 1, a cytokine which controls the production, differentiation, and function of macrophages. This receptor mediates most, if not all, of the biological effects of this cytokine. Ligand binding activates CSFR1 through a process of oligomerization and transphosphorylation. The encoded protein is a tyrosine kinase transmembrane receptor and member of the CSF1/PDGF receptor family of tyrosine-protein kinases.

Clinical significance

Mutations in CSF1R are associated with chronic myelomonocytic leukemia and type M4 acute myeloblastic leukemia.[3] Increased levels of CSF1R1 are found in microglia in Alzheimer's disease and after brain injuries. The increased receptor expression causes microglia to become more active.[4] Both CSF1R, and its ligand colony stimulating factor 1 play an important role in the development of the mammary gland and may be involved in the process of mammary gland carcinogenesis.[5][6][7] Mutations in the tyrosine kinase domain have been associated with hereditary diffuse leukoencephalopathy with spheroids.

Interactions

Colony stimulating factor 1 receptor has been shown to interact with:

See also


References

  1. ^ a b EntrezGene 1436
  2. ^ Galland F, Stefanova M, Lafage M, Birnbaum D (1992). "Localization of the 5' end of the MCF2 oncogene to human chromosome 15q15→q23". Cytogenet. Cell Genet. 60 (2): 114–6. doi:10.1159/000133316. PMID 1611909. 
  3. ^ Ridge SA, Worwood M, Oscier D, Jacobs A, Padua RA (February 1990). "FMS mutations in myelodysplastic, leukemic, and normal subjects". Proc. Natl. Acad. Sci. U.S.A. 87 (4): 1377–80. doi:10.1073/pnas.87.4.1377. JSTOR 2353838. PMC 53478. PMID 2406720. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=53478. 
  4. ^ Mitrasinovic OM, Grattan A, Robinson CC, Lapustea NB, Poon C, Ryan H, Phong C, Murphy GM (April 2005). "Microglia overexpressing the macrophage colony-stimulating factor receptor are neuroprotective in a microglial-hippocampal organotypic coculture system". J. Neurosci. 25 (17): 4442–51. doi:10.1523/JNEUROSCI.0514-05.2005. PMID 15858070. 
  5. ^ Tamimi RM, Brugge JS, Freedman ML, Miron A, Iglehart JD, Colditz GA, Hankinson SE (January 2008). "Circulating colony stimulating factor-1 and breast cancer risk". Cancer Res. 68 (1): 18–21. doi:10.1158/0008-5472.CAN-07-3234. PMC 2821592. PMID 18172291. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2821592. 
  6. ^ Pollard JW, Hennighausen L (September 1994). "Colony stimulating factor 1 is required for mammary gland development during pregnancy". Proc. Natl. Acad. Sci. U.S.A. 91 (20): 9312–6. doi:10.1073/pnas.91.20.9312. PMC 44802. PMID 7937762. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=44802. 
  7. ^ Sapi E (January 2004). "The role of CSF-1 in normal physiology of mammary gland and breast cancer: an update". Exp. Biol. Med. (Maywood) 229 (1): 1–11. PMID 14709771. http://ebm.rsmjournals.com/cgi/content/full/229/1/1. 
  8. ^ Mancini A, Koch A, Wilms R, Tamura T (April 2002). "c-Cbl associates directly with the C-terminal tail of the receptor for the macrophage colony-stimulating factor, c-Fms, and down-modulates this receptor but not the viral oncogene v-Fms". J. Biol. Chem. 277 (17): 14635–40. doi:10.1074/jbc.M109214200. PMID 11847211. 
  9. ^ Courtneidge SA, Dhand R, Pilat D, Twamley GM, Waterfield MD, Roussel MF (March 1993). "Activation of Src family kinases by colony stimulating factor-1, and their association with its receptor". EMBO J. 12 (3): 943–50. PMC 413295. PMID 7681396. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=413295. 
  10. ^ Mancini A, Niedenthal R, Joos H, Koch A, Trouliaris S, Niemann H, Tamura T (September 1997). "Identification of a second Grb2 binding site in the v-Fms tyrosine kinase". Oncogene 15 (13): 1565–72. doi:10.1038/sj.onc.1201518. PMID 9380408. 
  11. ^ Bourette RP, De Sepulveda P, Arnaud S, Dubreuil P, Rottapel R, Mouchiroud G (June 2001). "Suppressor of cytokine signaling 1 interacts with the macrophage colony-stimulating factor receptor and negatively regulates its proliferation signal". J. Biol. Chem. 276 (25): 22133–9. doi:10.1074/jbc.M101878200. PMID 11297560. 

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.