Colony stimulating factor 1 receptor: Difference between revisions

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{{Wikify|date=December 2007}}
{{Infobox_gene}}
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'''Colony stimulating factor 1 receptor''' ('''CSF1R'''), also known as '''macrophage colony-stimulating factor receptor''' (M-CSFR), and '''CD115''' ('''C'''luster of '''D'''ifferentiation '''115'''), is a cell-surface [[protein]] encoded, in humans, by the ''CSF1R'' [[gene]] (known also as c-FMS).<ref name="entrez">{{EntrezGene|1436}}</ref><ref name="pmid1611909">{{cite journal |vauthors=Galland F, Stefanova M, Lafage M, Birnbaum D | title = Localization of the 5' end of the MCF2 oncogene to human chromosome 15q15→q23 | journal = Cytogenet. Cell Genet. | volume = 60 | issue = 2 | pages = 114–6 | year = 1992 | pmid = 1611909 | doi = 10.1159/000133316 }}</ref> It is a [[Immune receptor|receptor]] for a [[cytokine]] called [[Macrophage colony-stimulating factor|colony stimulating factor 1]].
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
==Genomics==
{{GNF_Protein_box
| image =
| image_source =
| PDB =  
| Name = Colony stimulating factor 1 receptor, formerly McDonough feline sarcoma viral (v-fms) oncogene homolog
| HGNCid = 2433
| Symbol = CSF1R
| AltSymbols =; C-FMS; CD115; CSFR; FIM2; FMS
| OMIM = 164770
| ECnumber = 
| Homologene = 3817
| MGIid = 1339758
| GeneAtlas_image1 = PBB_GE_CSF1R_203104_at_tn.png
| Function = {{GNF_GO|id=GO:0000166 |text = nucleotide binding}} {{GNF_GO|id=GO:0004872 |text = receptor activity}} {{GNF_GO|id=GO:0005011 |text = macrophage colony stimulating factor receptor activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0005524 |text = ATP binding}} {{GNF_GO|id=GO:0016740 |text = transferase activity}}
| Component = {{GNF_GO|id=GO:0005886 |text = plasma membrane}} {{GNF_GO|id=GO:0005887 |text = integral to plasma membrane}}
| Process = {{GNF_GO|id=GO:0006468 |text = protein amino acid phosphorylation}} {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0007169 |text = transmembrane receptor protein tyrosine kinase signaling pathway}} {{GNF_GO|id=GO:0007275 |text = multicellular organismal development}} {{GNF_GO|id=GO:0008283 |text = cell proliferation}} {{GNF_GO|id=GO:0019735 |text = antimicrobial humoral response}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 1436
    | Hs_Ensembl = ENSG00000182578
    | Hs_RefseqProtein = NP_005202
    | Hs_RefseqmRNA = NM_005211
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 5
    | Hs_GenLoc_start = 149413051
    | Hs_GenLoc_end = 149473128
    | Hs_Uniprot = P07333
    | Mm_EntrezGene = 12978
    | Mm_Ensembl = ENSMUSG00000024621
    | Mm_RefseqmRNA = NM_001037859
    | Mm_RefseqProtein = NP_001032948
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 18
    | Mm_GenLoc_start = 61230941
    | Mm_GenLoc_end = 61256506
    | Mm_Uniprot = Q0P635
  }}
}}
'''Colony stimulating factor 1 receptor''' ('''CSF1R''') also known as '''CD115''' ('''C'''luster of '''D'''ifferentiation '''115'''), is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: CSF1R colony stimulating factor 1 receptor, formerly McDonough feline sarcoma viral (v-fms) oncogene homolog| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1436| accessdate = }}</ref>


The protein encoded by this gene is the receptor for colony stimulating factor 1, a [[cytokine]] which controls the production, differentiation, and function of [[macrophage]]s. This receptor mediates most if not all of the biological effects of this cytokine. [[Ligand (biochemistry)|Ligand]] binding activates this receptor kinase 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. Mutations in this gene have been associated with a predisposition to [[myeloid]] [[malignancy]]. The first intron of this gene contains a transcriptionally inactive ribosomal protein L7 processed pseudogene oriented in the opposite direction.<ref name="entrez">{{cite web | title = Entrez Gene: CSF1R colony stimulating factor 1 receptor, formerly McDonough feline sarcoma viral (v-fms) oncogene homolog| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1436| accessdate = }}</ref>
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 kilo[[Dalton (unit)|Dalton]]s. The first [[intron]] of the ''CSF1R'' gene contains a [[Transcription (genetics)|transcriptionally]] inactive [[RPL7|ribosomal protein L7]] processed [[pseudogene]], oriented in the opposite direction to the ''CSF1R'' gene.<ref name="entrez"/>
 
== Function ==
 
The encoded protein is a single pass type I membrane protein and acts as the receptor for [[macrophage colony-stimulating factor|colony stimulating factor 1]], a cytokine which controls the production, [[cell differentiation|differentiation]], and function of [[macrophage]]s. This receptor mediates most, if not all, of the biological effects of this cytokine. [[Ligand (biochemistry)|Ligand]] binding activates CSF1R through a process of [[oligomer]]ization and [[:wikt:trans-|trans-]][[phosphorylation]]. The encoded protein is a [[Receptor tyrosine kinase|tyrosine kinase]] [[transmembrane receptor]] and member of the CSF1/[[PDGF receptor]] family of tyrosine-protein kinases.<ref name="pmid26628682">{{cite journal | vauthors = Xu Q, Malecka KL, Fink L, Jordan EJ, Duffy E, Kolander S, Peterson JR, Dunbrack RL | title = Identifying three-dimensional structures of autophosphorylation complexes in crystals of protein kinases | journal = Science Signaling | volume = 8 | issue = 405 | pages = rs13 | year = 2015 | pmid = 26628682 | pmc = 4766099 | doi = 10.1126/scisignal.aaa6711 }}</ref><ref name="pmid20137931">{{cite journal | vauthors = Meyers MJ, Pelc M, Kamtekar S, Day J, Poda GI, Hall MK, Michener ML, Reitz BA, Mathis KJ, Pierce BS, Parikh MD, Mischke DA, Long SA, Parlow JJ, Anderson DR, Thorarensen A | display-authors = 6 | title = Structure-based drug design enables conversion of a DFG-in binding CSF-1R kinase inhibitor to a DFG-out binding mode | journal = Bioorganic & Medicinal Chemistry Letters | volume = 20 | issue = 5 | pages = 1543–7 | year = 2010 | pmid = 20137931 | doi = 10.1016/j.bmcl.2010.01.078 }}</ref>
 
== Clinical significance ==
 
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.<ref name="pmid15858070">{{cite journal |vauthors=Mitrasinovic OM, Grattan A, Robinson CC, Lapustea NB, Poon C, Ryan H, Phong C, Murphy GM | title = Microglia overexpressing the macrophage colony-stimulating factor receptor are neuroprotective in a microglial-hippocampal organotypic coculture system | journal = J. Neurosci. | volume = 25 | issue = 17 | pages = 4442–51 |date=April 2005 | pmid = 15858070 | doi = 10.1523/JNEUROSCI.0514-05.2005 }}</ref> Both CSF1R, and its ligand [[macrophage colony-stimulating factor|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]].<ref name="pmid18172291">{{cite journal |vauthors=Tamimi RM, Brugge JS, Freedman ML, Miron A, Iglehart JD, Colditz GA, Hankinson SE | title = Circulating colony stimulating factor-1 and breast cancer risk | journal = Cancer Res. | volume = 68 | issue = 1 | pages = 18–21 |date=January 2008 | pmid = 18172291 | pmc = 2821592 | doi = 10.1158/0008-5472.CAN-07-3234 }}</ref><ref name="pmid7937762">{{cite journal |vauthors=Pollard JW, Hennighausen L | title = Colony stimulating factor 1 is required for mammary gland development during pregnancy | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 91 | issue = 20 | pages = 9312–6 |date=September 1994 | pmid = 7937762 | pmc = 44802 | doi = 10.1073/pnas.91.20.9312 }}</ref><ref name="pmid14709771">{{cite journal | author = Sapi E | title = The role of CSF-1 in normal physiology of mammary gland and breast cancer: an update | journal = Exp. Biol. Med. (Maywood) | volume = 229 | issue = 1 | pages = 1–11 |date=January 2004 | pmid = 14709771 | doi = | url = http://ebm.rsmjournals.com/cgi/content/full/229/1/1 }}</ref>
 
Mutations in CSF1R are associated with [[chronic myelomonocytic leukemia]] and type M4 [[acute myeloblastic leukemia]].<ref name="pmid2406720">{{cite journal |vauthors=Ridge SA, Worwood M, Oscier D, Jacobs A, Padua RA | title = FMS mutations in myelodysplastic, leukemic, and normal subjects | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 87 | issue = 4 | pages = 1377–80 |date=February 1990 | pmid = 2406720 | pmc = 53478 | doi = 10.1073/pnas.87.4.1377 | jstor = 2353838 }}</ref>
 
Mutations in the tyrosine kinase domain have been associated with [[hereditary diffuse leukoencephalopathy with spheroids]].
 
===As a drug target===
Because CSF1R is overexpressed in many cancers and on [[tumor-associated macrophage]]s, '''CSF1R inhibitors''' have been studied for many years as a possible treatment for cancer or inflammatory diseases.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/19689368 ''Colony-stimulating factor-1 receptor inhibitors for the treatment of cancer and inflammatory disease.'' 2009]</ref><ref name="Cannarile_2017">{{cite journal | vauthors = Cannarile MA, Weisser M, Jacob W, Jegg AM, Ries CH, Rüttinger D | title = Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy | journal = Journal for Immunotherapy of Cancer | volume = 5 | issue = 1 | pages = 53 | year = 2017 | pmid = 28716061 | pmc = 5514481 | doi = 10.1186/s40425-017-0257-y }}</ref>  {{as of|2017}} CSF1R inhibitors in clinical trials include :<ref name="Cannarile_2017" /> [[Pexidartinib]], [[PLX7486]], [[ARRY-382]], [[JNJ-40346527]],<ref name="pmid26233509">{{cite journal | vauthors = Genovese MC, Hsia E, Belkowski SM, Chien C, Masterson T, Thurmond RL, Manthey CL, Yan XD, Ge T, Franks C, Greenspan A | title = Results from a Phase IIA Parallel Group Study of JNJ-40346527, an Oral CSF-1R Inhibitor, in Patients with Active Rheumatoid Arthritis despite Disease-modifying Antirheumatic Drug Therapy | journal = The Journal of Rheumatology | volume = 42 | issue = 10 | pages = 1752–60 | year = 2015 | pmid = 26233509 | doi = 10.3899/jrheum.141580 }}</ref> [[BLZ945]], [[Emactuzumab]], [[AMG820]], [[IMC-CS4]]. ([[MCS110]] is a CSF1 inhibitor)
 
Another CSF1R inhibitor that targets/depletes TAMs is [[Cabiralizumab]] (cabira; FPA-008) which is a [[monoclonal antibody]]<ref>[http://ascopubs.org/doi/abs/10.1200/JCO.2017.35.15_suppl.11078 A phase I/II dose escalation and expansion study of cabiralizumab (cabira; FPA-008), an anti-CSF1R antibody, in tenosynovial giant cell tumor (TGCT, diffuse pigmented villonodular synovitis D-PVNS).]</ref> and is in early clinical trials for metastatic pancreatic cancer.<ref>[https://clinicaltrials.gov/ct2/show/NCT03158272 A Study to of Cabiralzumab Given by Itself or With Nivolumab in Advanced Cancer or Cancer That Has Spread]</ref><ref>[http://www.onclive.com/web-exclusives/novel-combination-shows-promising-responses-in-pancreatic-cancer ''Novel Combination Shows Promising Responses in Pancreatic Cancer'' Nov 2017]</ref>
 
==Interactions==
Colony stimulating factor 1 receptor has been shown to [[Protein-protein interaction|interact]] with:
* [[Cbl gene]],<ref name="pmid11847211">{{cite journal |vauthors=Mancini A, Koch A, Wilms R, Tamura T | title = 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 | journal = J. Biol. Chem. | volume = 277 | issue = 17 | pages = 14635–40 |date=April 2002 | pmid = 11847211 | doi = 10.1074/jbc.M109214200 }}</ref>
* [[FYN]],<ref name="pmid7681396">{{cite journal |vauthors=Courtneidge SA, Dhand R, Pilat D, Twamley GM, Waterfield MD, Roussel MF | title = Activation of Src family kinases by colony stimulating factor-1, and their association with its receptor | journal = EMBO J. | volume = 12 | issue = 3 | pages = 943–50 |date=March 1993 | pmid = 7681396 | pmc = 413295 | doi = }}</ref>
* [[Grb2]],<ref name="pmid9380408">{{cite journal |vauthors=Mancini A, Niedenthal R, Joos H, Koch A, Trouliaris S, Niemann H, Tamura T | title = Identification of a second Grb2 binding site in the v-Fms tyrosine kinase | journal = Oncogene | volume = 15 | issue = 13 | pages = 1565–72 |date=September 1997 | pmid = 9380408 | doi = 10.1038/sj.onc.1201518 | url = }}</ref>
* [[Suppressor of cytokine signaling 1]],<ref name="pmid11297560">{{cite journal |vauthors=Bourette RP, De Sepulveda P, Arnaud S, Dubreuil P, Rottapel R, Mouchiroud G | title = Suppressor of cytokine signaling 1 interacts with the macrophage colony-stimulating factor receptor and negatively regulates its proliferation signal | journal = J. Biol. Chem. | volume = 276 | issue = 25 | pages = 22133–9 |date=June 2001 | pmid = 11297560 | doi = 10.1074/jbc.M101878200 }}</ref> This receptor is also linked with the cells of MPS.


==See also==
==See also==
* [[Cluster of differentiation]]
* [[Cluster of differentiation]]
* [[Mouse models of breast cancer metastasis]]
{{Clear}}


==References==
==References==
{{reflist|2}}
{{reflist|colwidth=35em}}


==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin|colwidth=35em}}
{{PBB_Further_reading
* {{cite journal |vauthors=Rettenmier CW, Roussel MF, Sherr CJ | title = The colony-stimulating factor 1 (CSF-1) receptor (c-fms proto-oncogene product) and its ligand | journal = J. Cell Sci. Suppl. | volume = 9 | issue = | pages = 27–44 | year = 1988 | pmid = 2978516 | doi = }}
| citations =
* {{cite journal |vauthors=Stanley ER, Berg KL, Einstein DB, Lee PS, Pixley FJ, Wang Y, Yeung YG | title = Biology and action of colony--stimulating factor-1 | journal = Mol. Reprod. Dev. | volume = 46 | issue = 1 | pages = 4–10 |date=January 1997 | pmid = 8981357 | doi = 10.1002/(SICI)1098-2795(199701)46:1<4::AID-MRD2>3.0.CO;2-V }}
*{{cite journal | author=Rettenmier CW, Roussel MF, Sherr CJ |title=The colony-stimulating factor 1 (CSF-1) receptor (c-fms proto-oncogene product) and its ligand. |journal=J. Cell Sci. Suppl. |volume=9 |issue= |pages= 27-44 |year= 1989 |pmid= 2978516 |doi= }}
* {{cite journal |vauthors=Gout I, Dhand R, Panayotou G, Fry MJ, Hiles I, Otsu M, Waterfield MD | title = Expression and characterization of the p85 subunit of the phosphatidylinositol 3-kinase complex and a related p85 beta protein by using the baculovirus expression system | journal = Biochem. J. | volume = 288 | issue = 2| pages = 395–405 |date=December 1992 | pmid = 1334406 | pmc = 1132024 | doi = 10.1042/bj2880395}}
*{{cite journal | author=Stanley ER, Berg KL, Einstein DB, ''et al.'' |title=Biology and action of colony--stimulating factor-1. |journal=Mol. Reprod. Dev. |volume=46 |issue= 1 |pages= 4-10 |year= 1997 |pmid= 8981357 |doi= 10.1002/(SICI)1098-2795(199701)46:1<4::AID-MRD2>3.0.CO;2-V }}
* {{cite journal |vauthors=Boultwood J, Rack K, Kelly S, Madden J, Sakaguchi AY, Wang LM, Oscier DG, Buckle VJ, Wainscoat JS | title = Loss of both CSF1R (FMS) alleles in patients with myelodysplasia and a chromosome 5 deletion | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 88 | issue = 14 | pages = 6176–80 |date=July 1991 | pmid = 1829836 | pmc = 52045 | doi = 10.1073/pnas.88.14.6176 }}
*{{cite journal | author=Gout I, Dhand R, Panayotou G, ''et al.'' |title=Expression and characterization of the p85 subunit of the phosphatidylinositol 3-kinase complex and a related p85 beta protein by using the baculovirus expression system. |journal=Biochem. J. |volume=288 ( Pt 2) |issue= |pages= 395-405 |year= 1993 |pmid= 1334406 |doi= }}
* {{cite journal |vauthors=Roussel MF, Cleveland JL, Shurtleff SA, Sherr CJ | title = Myc rescue of a mutant CSF-1 receptor impaired in mitogenic signalling | journal = Nature | volume = 353 | issue = 6342 | pages = 361–3 |date=September 1991 | pmid = 1833648 | doi = 10.1038/353361a0 }}
*{{cite journal  | author=Galland F, Stefanova M, Lafage M, Birnbaum D |title=Localization of the 5' end of the MCF2 oncogene to human chromosome 15q15----q23. |journal=Cytogenet. Cell Genet. |volume=60 |issue= 2 |pages= 114-6 |year= 1992 |pmid= 1611909 |doi=  }}
* {{cite journal |vauthors=Reedijk M, Liu XQ, Pawson T | title = Interactions of phosphatidylinositol kinase, GTPase-activating protein (GAP), and GAP-associated proteins with the colony-stimulating factor 1 receptor | journal = Mol. Cell. Biol. | volume = 10 | issue = 11 | pages = 5601–8 |date=November 1990 | pmid = 2172781 | pmc = 361316 | doi = }}
*{{cite journal | author=Boultwood J, Rack K, Kelly S, ''et al.'' |title=Loss of both CSF1R (FMS) alleles in patients with myelodysplasia and a chromosome 5 deletion. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=88 |issue= 14 |pages= 6176-80 |year= 1991 |pmid= 1829836 |doi= }}
* {{cite journal |vauthors=Sherr CJ, Rettenmier CW, Sacca R, Roussel MF, Look AT, Stanley ER | title = The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1 | journal = Cell | volume = 41 | issue = 3 | pages = 665–76 |date=July 1985 | pmid = 2408759 | doi = 10.1016/S0092-8674(85)80047-7 }}
*{{cite journal | author=Roussel MF, Cleveland JL, Shurtleff SA, Sherr CJ |title=Myc rescue of a mutant CSF-1 receptor impaired in mitogenic signalling. |journal=Nature |volume=353 |issue= 6342 |pages= 361-3 |year= 1991 |pmid= 1833648 |doi= 10.1038/353361a0 }}
* {{cite journal |vauthors=Coussens L, Van Beveren C, Smith D, Chen E, Mitchell RL, Isacke CM, Verma IM, Ullrich A | title = Structural alteration of viral homologue of receptor proto-oncogene fms at carboxyl terminus | journal = Nature | volume = 320 | issue = 6059 | pages = 277–80 | year = 1986 | pmid = 2421165 | doi = 10.1038/320277a0 }}
*{{cite journal | author=Reedijk M, Liu XQ, Pawson T |title=Interactions of phosphatidylinositol kinase, GTPase-activating protein (GAP), and GAP-associated proteins with the colony-stimulating factor 1 receptor. |journal=Mol. Cell. Biol. |volume=10 |issue= 11 |pages= 5601-8 |year= 1990 |pmid= 2172781 |doi= }}
* {{cite journal |vauthors=Hampe A, Shamoon BM, Gobet M, Sherr CJ, Galibert F | title = Nucleotide sequence and structural organization of the human FMS proto-oncogene | journal = Oncogene Res. | volume = 4 | issue = 1 | pages = 9–17 | year = 1989 | pmid = 2524025 | doi = }}
*{{cite journal  | author=Ridge SA, Worwood M, Oscier D, ''et al.'' |title=FMS mutations in myelodysplastic, leukemic, and normal subjects. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=87 |issue= 4 |pages= 1377-80 |year= 1990 |pmid= 2406720 |doi= }}
* {{cite journal |vauthors=Visvader J, Verma IM | title = Differential transcription of exon 1 of the human c-fms gene in placental trophoblasts and monocytes | journal = Mol. Cell. Biol. | volume = 9 | issue = 3 | pages = 1336–41 |date=March 1989 | pmid = 2524648 | pmc = 362728 | doi = }}
*{{cite journal | author=Sherr CJ, Rettenmier CW, Sacca R, ''et al.'' |title=The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. |journal=Cell |volume=41 |issue= 3 |pages= 665-76 |year= 1985 |pmid= 2408759 |doi= }}
* {{cite journal |vauthors=Roberts WM, Look AT, Roussel MF, Sherr CJ | title = Tandem linkage of human CSF-1 receptor (c-fms) and PDGF receptor genes | journal = Cell | volume = 55 | issue = 4 | pages = 655–61 |date=November 1988 | pmid = 2846185 | doi = 10.1016/0092-8674(88)90224-3 }}
*{{cite journal | author=Coussens L, Van Beveren C, Smith D, ''et al.'' |title=Structural alteration of viral homologue of receptor proto-oncogene fms at carboxyl terminus. |journal=Nature |volume=320 |issue= 6059 |pages= 277-80 |year= 1986 |pmid= 2421165 |doi= 10.1038/320277a0 }}
* {{cite journal |vauthors=Xu DQ, Guilhot S, Galibert F | title = Restriction fragment length polymorphism of the human c-fms gene | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 82 | issue = 9 | pages = 2862–5 |date=May 1985 | pmid = 2986142 | pmc = 397666 | doi = 10.1073/pnas.82.9.2862 | jstor = 25278 }}
*{{cite journal | author=Hampe A, Shamoon BM, Gobet M, ''et al.'' |title=Nucleotide sequence and structural organization of the human FMS proto-oncogene. |journal=Oncogene Res. |volume=4 |issue= 1 |pages= 9-17 |year= 1989 |pmid= 2524025 |doi= }}
* {{cite journal |vauthors=Sherr CJ, Rettenmier CW | title = The fms gene and the CSF-1 receptor | journal = Cancer Surv. | volume = 5 | issue = 2 | pages = 221–32 | year = 1986 | pmid = 3022923 | doi = | url = }}
*{{cite journal | author=Visvader J, Verma IM |title=Differential transcription of exon 1 of the human c-fms gene in placental trophoblasts and monocytes. |journal=Mol. Cell. Biol. |volume=9 |issue= 3 |pages= 1336-41 |year= 1989 |pmid= 2524648 |doi= }}
* {{cite journal |vauthors=Le Beau MM, Westbrook CA, Diaz MO, Larson RA, Rowley JD, Gasson JC, Golde DW, Sherr CJ | title = Evidence for the involvement of GM-CSF and FMS in the deletion (5q) in myeloid disorders | journal = Science | volume = 231 | issue = 4741 | pages = 984–7 |date=February 1986 | pmid = 3484837 | doi = 10.1126/science.3484837 }}
*{{cite journal | author=Roberts WM, Look AT, Roussel MF, Sherr CJ |title=Tandem linkage of human CSF-1 receptor (c-fms) and PDGF receptor genes. |journal=Cell |volume=55 |issue= 4 |pages= 655-61 |year= 1988 |pmid= 2846185 |doi= }}
* {{cite journal |vauthors=Wheeler EF, Roussel MF, Hampe A, Walker MH, Fried VA, Look AT, Rettenmier CW, Sherr CJ | title = The amino-terminal domain of the v-fms oncogene product includes a functional signal peptide that directs synthesis of a transforming glycoprotein in the absence of feline leukemia virus gag sequences | journal = J. Virol. | volume = 59 | issue = 2 | pages = 224–33 |date=August 1986 | pmid = 3525854 | pmc = 253070 | dpi =  }}
*{{cite journal | author=Xu DQ, Guilhot S, Galibert F |title=Restriction fragment length polymorphism of the human c-fms gene. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=82 |issue= 9 |pages= 2862-5 |year= 1985 |pmid= 2986142 |doi= }}
* {{cite journal |vauthors=Verbeek JS, Roebroek AJ, van den Ouweland AM, Bloemers HP, Van de Ven WJ | title = Human c-fms proto-oncogene: comparative analysis with an abnormal allele | journal = Mol. Cell. Biol. | volume = 5 | issue = 2 | pages = 422–6 |date=February 1985 | pmid = 3974576 | pmc = 366728 | dpi =  }}
*{{cite journal | author=Sherr CJ, Rettenmier CW |title=The fms gene and the CSF-1 receptor. |journal=Cancer Surv. |volume=5 |issue= 2 |pages= 221-32 |year= 1987 |pmid= 3022923 |doi= }}
* {{cite journal |vauthors=Lee AW, Nienhuis AW | title = Mechanism of kinase activation in the receptor for colony-stimulating factor 1 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 87 | issue = 18 | pages = 7270–4 |date=September 1990 | pmid = 2169623 | pmc = 54725 | doi = 10.1073/pnas.87.18.7270 }}
*{{cite journal | author=Le Beau MM, Westbrook CA, Diaz MO, ''et al.'' |title=Evidence for the involvement of GM-CSF and FMS in the deletion (5q) in myeloid disorders. |journal=Science |volume=231 |issue= 4741 |pages= 984-7 |year= 1986 |pmid= 3484837 |doi= }}
*{{cite journal | author=Wheeler EF, Roussel MF, Hampe A, ''et al.'' |title=The amino-terminal domain of the v-fms oncogene product includes a functional signal peptide that directs synthesis of a transforming glycoprotein in the absence of feline leukemia virus gag sequences. |journal=J. Virol. |volume=59 |issue= 2 |pages= 224-33 |year= 1986 |pmid= 3525854 |doi=  }}
*{{cite journal | author=Browning PJ, Bunn HF, Cline A, ''et al.'' |title="Replacement" of COOH-terminal truncation of v-fms with c-fms sequences markedly reduces transformation potential. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=83 |issue= 20 |pages= 7800-4 |year= 1986 |pmid= 3532121 |doi=  }}
*{{cite journal | author=Verbeek JS, Roebroek AJ, van den Ouweland AM, ''et al.'' |title=Human c-fms proto-oncogene: comparative analysis with an abnormal allele. |journal=Mol. Cell. Biol. |volume=5 |issue= 2 |pages= 422-6 |year= 1985 |pmid= 3974576 |doi= }}
}}
{{refend}}
{{refend}}


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* {{MeshName|CSF1R+protein,+human}}
* {{MeshName|CSF1R+protein,+human}}


{{membrane-protein-stub}}
{{NLM content}}
{{NLM content}}
{{Clusters of differentiation}}
{{Clusters of differentiation}}
{{Immune receptors}}
{{Cytokine receptors}}
{{Tyrosine kinases}}
{{Enzymes}}
{{Cytokine receptor modulators}}
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[[Category:Clusters of differentiation]]
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[[Category:Cytokine receptors]]
[[Category:Immunoglobulin superfamily cytokine receptors]]
[[Category:Tyrosine kinase receptors]]

Revision as of 14:06, 25 November 2017

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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 (known also as c-FMS).[1][2] It is a receptor for a cytokine called colony stimulating factor 1.

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 CSF1R gene contains a transcriptionally inactive ribosomal protein L7 processed pseudogene, oriented in the opposite direction to the CSF1R gene.[1]

Function

The encoded 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 CSF1R through a process of oligomerization and trans-phosphorylation. The encoded protein is a tyrosine kinase transmembrane receptor and member of the CSF1/PDGF receptor family of tyrosine-protein kinases.[3][4]

Clinical significance

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.[5] 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.[6][7][8]

Mutations in CSF1R are associated with chronic myelomonocytic leukemia and type M4 acute myeloblastic leukemia.[9]

Mutations in the tyrosine kinase domain have been associated with hereditary diffuse leukoencephalopathy with spheroids.

As a drug target

Because CSF1R is overexpressed in many cancers and on tumor-associated macrophages, CSF1R inhibitors have been studied for many years as a possible treatment for cancer or inflammatory diseases.[10][11] As of 2017 CSF1R inhibitors in clinical trials include :[11] Pexidartinib, PLX7486, ARRY-382, JNJ-40346527,[12] BLZ945, Emactuzumab, AMG820, IMC-CS4. (MCS110 is a CSF1 inhibitor)

Another CSF1R inhibitor that targets/depletes TAMs is Cabiralizumab (cabira; FPA-008) which is a monoclonal antibody[13] and is in early clinical trials for metastatic pancreatic cancer.[14][15]

Interactions

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

See also

References

  1. ↑ 1.0 1.1 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. ↑ Xu Q, Malecka KL, Fink L, Jordan EJ, Duffy E, Kolander S, Peterson JR, Dunbrack RL (2015). "Identifying three-dimensional structures of autophosphorylation complexes in crystals of protein kinases". Science Signaling. 8 (405): rs13. doi:10.1126/scisignal.aaa6711. PMC 4766099. PMID 26628682.
  4. ↑ Meyers MJ, Pelc M, Kamtekar S, Day J, Poda GI, Hall MK, et al. (2010). "Structure-based drug design enables conversion of a DFG-in binding CSF-1R kinase inhibitor to a DFG-out binding mode". Bioorganic & Medicinal Chemistry Letters. 20 (5): 1543–7. doi:10.1016/j.bmcl.2010.01.078. PMID 20137931.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ Colony-stimulating factor-1 receptor inhibitors for the treatment of cancer and inflammatory disease. 2009
  11. ↑ 11.0 11.1 Cannarile MA, Weisser M, Jacob W, Jegg AM, Ries CH, Rüttinger D (2017). "Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy". Journal for Immunotherapy of Cancer. 5 (1): 53. doi:10.1186/s40425-017-0257-y. PMC 5514481. PMID 28716061.
  12. ↑ Genovese MC, Hsia E, Belkowski SM, Chien C, Masterson T, Thurmond RL, Manthey CL, Yan XD, Ge T, Franks C, Greenspan A (2015). "Results from a Phase IIA Parallel Group Study of JNJ-40346527, an Oral CSF-1R Inhibitor, in Patients with Active Rheumatoid Arthritis despite Disease-modifying Antirheumatic Drug Therapy". The Journal of Rheumatology. 42 (10): 1752–60. doi:10.3899/jrheum.141580. PMID 26233509.
  13. ↑ A phase I/II dose escalation and expansion study of cabiralizumab (cabira; FPA-008), an anti-CSF1R antibody, in tenosynovial giant cell tumor (TGCT, diffuse pigmented villonodular synovitis D-PVNS).
  14. ↑ A Study to of Cabiralzumab Given by Itself or With Nivolumab in Advanced Cancer or Cancer That Has Spread
  15. ↑ Novel Combination Shows Promising Responses in Pancreatic Cancer Nov 2017
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ 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.

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