Protein-coding gene in the species Homo sapiens
Thegranulocyte colony-stimulating factor receptor (G-CSF-R ) also known asCD114 (C luster ofD ifferentiation114 ) is aprotein that in humans is encoded by theCSF3R gene .[ 5] cell -surfacereceptor for thegranulocyte colony-stimulating factor (G-CSF).[ 6] cytokine receptors known as thehematopoietin receptor familybone marrow , and, in response to stimulation by G-CSF, initiatescell proliferation anddifferentiation into mature neutrophilicgranulocytes andmacrophages .
The G-CSF-R is atransmembrane receptor that consists of an extracellular ligand-binding portion, atransmembrane domain , and the cytoplasmic portion that is responsible forsignal transduction . GCSF-R ligand-binding is associated withdimerization of the receptor and signal transduction through proteins includingJak ,Lyn ,STAT , andErk1/2 .
The class IV isoform defective for both internalization and differentiation signaling,[ 7]
Clinical significance [ edit ] Mutations in this gene are a cause of Kostmann syndrome, also known assevere congenital neutropenia .[ 8]
Mutations in the intracellular part of this receptor are also associated with certain types ofleukemia .[ 9]
In clinical medicine, there is a suggestion that use ofGCSF should be avoided, at least in children and adolescents and perhaps adults, when G-CSFR isoform IV is overexpressed.[ 10]
Granulocyte colony-stimulating factor receptor has been shown tointeract withGrb2 ,[ 11] HCK [ 12] SHC1 .[ 11]
^a b c GRCh38: Ensembl release 89: ENSG00000119535 –Ensembl , May 2017^a b c GRCm38: Ensembl release 89: ENSMUSG00000028859 –Ensembl , May 2017^ "Human PubMed Reference:" .National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" .National Center for Biotechnology Information, U.S. National Library of Medicine .^ Tweardy DJ, Anderson K, Cannizzaro LA, Steinman RA, Croce CM, Huebner K (March 1992)."Molecular cloning of cDNAs for the human granulocyte colony-stimulating factor receptor from HL-60 and mapping of the gene to chromosome region 1p32-34" .Blood .79 (5):1148– 54.doi :10.1182/blood.V79.5.1148.1148 PMID 1371413 . ^ "Entrez Gene: CSF3R colony stimulating factor 3 receptor (granulocyte)" .^ Mehta HM, Futami M, Glaubach T, Lee DW, Andolina JR, Yang Q, et al. (May 2014)."Alternatively spliced, truncated GCSF receptor promotes leukemogenic properties and sensitivity to JAK inhibition" .Leukemia .28 (5):1041– 1051.doi :10.1038/leu.2013.321 .PMC 5875430 PMID 24170028 . ^ Zeidler C, Welte K (April 2002). "Kostmann syndrome and severe congenital neutropenia".Semin. Hematol .39 (2):82– 8.doi :10.1053/shem.2002.31913 .PMID 11957189 . ^ Beekman R, Touw IP (June 2010)."G-CSF and its receptor in myeloid malignancy" .Blood .115 (25):5131– 6.doi :10.1182/blood-2010-01-234120 PMID 20237318 . ^ Ehlers S, Herbst C, Zimmermann M, Scharn N, Germeshausen M, von Neuhoff N, et al. (May 2010)."Granulocyte colony-stimulating factor (G-CSF) treatment of childhood acute myeloid leukemias that overexpress the differentiation-defective G-CSF receptor isoform IV is associated with a higher incidence of relapse" .J. Clin. Oncol .28 (15):2591– 7.doi :10.1200/JCO.2009.25.9010 PMID 20406937 . ^a b Ward AC, Monkhouse JL, Hamilton JA, Csar XF (November 1998)."Direct binding of Shc, Grb2, SHP-2 and p40 to the murine granulocyte colony-stimulating factor receptor" .Biochim. Biophys. Acta .1448 (1):70– 6.doi :10.1016/S0167-4889(98)00120-7 hdl :10536/DRO/DU:30096477 PMID 9824671 . ^ Ward AC, Monkhouse JL, Csar XF, Touw IP, Bello PA (October 1998). "The Src-like tyrosine kinase Hck is activated by granulocyte colony-stimulating factor (G-CSF) and docks to the activated G-CSF receptor".Biochem. Biophys. Res. Commun .251 (1):117– 23.Bibcode :1998BBRC..251..117W .doi :10.1006/bbrc.1998.9441 .PMID 9790917 . Tsuji K, Ebihara Y (2002). "Expression of G-CSF receptor on myeloid progenitors".Leuk. Lymphoma .42 (6):1351– 7.doi :10.3109/10428190109097763 .PMID 11911419 .S2CID 8010177 . Kimura A, Sultana TA (2005). "Granulocyte colony-stimulating factor receptors on CD34++ cells in patients with myelodysplastic syndrome (MDS) and MDS-acute myeloid leukemia".Leuk. Lymphoma .45 (10):1995– 2000.doi :10.1080/10428190410001714034 .PMID 15370243 .S2CID 36625508 . Tweardy DJ, Anderson K, Cannizzaro LA, Steinman RA, Croce CM, Huebner K (1992)."Molecular cloning of cDNAs for the human granulocyte colony-stimulating factor receptor from HL-60 and mapping of the gene to chromosome region 1p32-34" .Blood .79 (5):1148– 54.doi :10.1182/blood.V79.5.1148.1148 PMID 1371413 . Seto Y, Fukunaga R, Nagata S (1992)."Chromosomal gene organization of the human granulocyte colony-stimulating factor receptor" .J. Immunol .148 (1):259– 66.doi :10.4049/jimmunol.148.1.259 PMID 1530796 . Fukunaga R, Seto Y, Mizushima S, Nagata S (1991)."Three different mRNAs encoding human granulocyte colony-stimulating factor receptor" .Proc. Natl. Acad. Sci. U.S.A .87 (22):8702– 6.doi :10.1073/pnas.87.22.8702 PMC 55027 PMID 1701053 . Fukunaga R, Ishizaka-Ikeda E, Pan CX, Seto Y, Nagata S (1991)."Functional domains of the granulocyte colony-stimulating factor receptor" .EMBO J .10 (10):2855– 65.doi :10.1002/j.1460-2075.1991.tb07835.x .PMC 452996 PMID 1717255 . Inazawa J, Fukunaga R, Seto Y, Nakagawa H, Misawa S, Abe T, et al. (1991). "Assignment of the human granulocyte colony-stimulating factor receptor gene (CSF3R) to chromosome 1 at region p35-p34.3".Genomics .10 (4):1075– 8.doi :10.1016/0888-7543(91)90202-P .PMID 1833306 . Larsen A, Davis T, Curtis BM, Gimpel S, Sims JE, Cosman D, et al. (1991)."Expression cloning of a human granulocyte colony-stimulating factor receptor: a structural mosaic of hematopoietin receptor, immunoglobulin, and fibronectin domains" .J. Exp. Med .172 (6):1559– 70.doi :10.1084/jem.172.6.1559 .PMC 2188748 PMID 2147944 . Uzumaki H, Okabe T, Sasaki N, Hagiwara K, Takaku F, Tobita M, et al. (1990)."Identification and characterization of receptors for granulocyte colony-stimulating factor on human placenta and trophoblastic cells" .Proc. Natl. Acad. Sci. U.S.A .86 (23):9323– 6.doi :10.1073/pnas.86.23.9323 PMC 298487 PMID 2480598 . Nicholson SE, Oates AC, Harpur AG, Ziemiecki A, Wilks AF, Layton JE (1994)."Tyrosine kinase JAK1 is associated with the granulocyte-colony-stimulating factor receptor and both become tyrosine-phosphorylated after receptor activation" .Proc. Natl. Acad. Sci. U.S.A .91 (8):2985– 8.Bibcode :1994PNAS...91.2985N .doi :10.1073/pnas.91.8.2985 PMC 43499 PMID 7512720 . Dong F, Hoefsloot LH, Schelen AM, Broeders CA, Meijer Y, Veerman AJ, et al. (1994)."Identification of a nonsense mutation in the granulocyte-colony-stimulating factor receptor in severe congenital neutropenia" .Proc. Natl. Acad. Sci. U.S.A .91 (10):4480– 4.Bibcode :1994PNAS...91.4480D .doi :10.1073/pnas.91.10.4480 PMC 43809 PMID 7514305 . Dong F, Brynes RK, Tidow N, Welte K, Löwenberg B, Touw IP (1995)."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 .333 (8):487– 93.doi :10.1056/NEJM199508243330804 .hdl :1765/60338 PMID 7542747 . Shimoda K, Okamura S, Harada N, Kondo S, Okamura T, Niho Y (1993)."Identification of a functional receptor for granulocyte colony-stimulating factor on platelets" .J. Clin. Invest .91 (4):1310– 3.doi :10.1172/JCI116330 .PMC 288100 PMID 7682568 . Zhao Y, Wagner F, Frank SJ, Kraft AS (1995)."The amino-terminal portion of the JAK2 protein kinase is necessary for binding and phosphorylation of the granulocyte-macrophage colony-stimulating factor receptor beta c chain" .J. Biol. Chem .270 (23):13814– 8.doi :10.1074/jbc.270.23.13814 PMID 7775438 . Corey SJ, Burkhardt AL, Bolen JB, Geahlen RL, Tkatch LS, Tweardy DJ (1994)."Granulocyte colony-stimulating factor receptor signaling involves the formation of a three-component complex with Lyn and Syk protein-tyrosine kinases" .Proc. Natl. Acad. Sci. U.S.A .91 (11):4683– 7.Bibcode :1994PNAS...91.4683C .doi :10.1073/pnas.91.11.4683 PMC 43852 PMID 8197119 . Haniu M, Horan T, Arakawa T, Le J, Katta V, Rohde MF (1996). "Extracellular domain of granulocyte-colony stimulating factor receptor. Interaction with its ligand and identification of a domain in close proximity of ligand-binding region".Arch. Biochem. Biophys .324 (2):344– 56.doi :10.1006/abbi.1995.0047 .PMID 8554326 . Horan T, Wen J, Narhi L, Parker V, Garcia A, Arakawa T, et al. (1996). "Dimerization of the extracellular domain of granuloycte-colony stimulating factor receptor by ligand binding: a monovalent ligand induces 2:2 complexes".Biochemistry .35 (15):4886– 96.doi :10.1021/bi9525841 .PMID 8664280 . McCracken S, Layton JE, Shorter SC, Starkey PM, Barlow DH, Mardon HJ (1996). "Expression of granulocyte-colony stimulating factor and its receptor is regulated during the development of the human placenta".J. Endocrinol .149 (2):249– 58.doi :10.1677/joe.0.1490249 .PMID 8708536 . Haniu M, Horan T, Arakawa T, Le J, Katta V, Hara S, et al. (1996). "Disulfide structure and N-glycosylation sites of an extracellular domain of granulocyte-colony stimulating factor receptor".Biochemistry .35 (40):13040– 6.doi :10.1021/bi960213u .PMID 8855939 . Bonaldo MF, Lennon G, Soares MB (1997)."Normalization and subtraction: two approaches to facilitate gene discovery" .Genome Res .6 (9):791– 806.doi :10.1101/gr.6.9.791 PMID 8889548 .
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Chemokine CSF
Interferon
IFNAR (α/β, I) Agonists: Albinterferon Interferon alpha (interferon alfa, IFN-α) Interferon alfa (IFNA1 ,IFNA2 ,IFNA4 ,IFNA5 ,IFNA6 ,IFNA7 ,IFNA8 ,IFNA10 ,IFNA13 ,IFNA14 ,IFNA16 ,IFNA17 ,IFNA21 )Interferon alfa 2a Interferon alfa 2b Interferon alfa n1 Interferon alfacon-1 Interferon alpha-n3 Interferon beta (IFN-β) (IFNB1 ,IFNB3 )Interferon beta 1a Interferon beta 1b Interferon kappa (IFN-ε/κ/τ/ζ, IFNK) Interferon omega (IFN-ω, IFNW1) Peginterferon alfa-2a Peginterferon alfa-2b IFNGR (γ, II) IFNLR (λ, III) See IL-28R (IFNLR)here instead.
Interleukin TGFβ TNF Others
