Granulocyte colony-stimulating factor receptor

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Species	Human	Mouse
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The granulocyte colony-stimulating factor receptor (G-CSF-R) also known as CD114 (Cluster of Differentiation 114) is a protein that in humans is encoded by the CSF3R gene. G-CSF-R is a cell-surface receptor for the granulocyte colony-stimulating factor (G-CSF). The G-CSF receptors belongs to a family of cytokine receptors known as the hematopoietin receptor family. The granulocyte colony-stimulating factor receptor is present on precursor cells in the bone marrow, and, in response to stimulation by G-CSF, initiates cell proliferation and differentiation into mature neutrophilic granulocytes and macrophages.

The G-CSF-R is a transmembrane receptor that consists of an extracellular ligand-binding portion, a transmembrane domain, and the cytoplasmic portion that is responsible for signal transduction. GCSF-R ligand-binding is associated with dimerization of the receptor and signal transduction through proteins including Jak, Lyn, STAT, and Erk1/2.

Isoforms

The class IV isoform defective for both internalization and differentiation signaling.

Clinical significance

Mutations in this gene are a cause of Kostmann syndrome, also known as severe congenital neutropenia.

Mutations in the intracellular part of this receptor are also associated with certain types of leukemia.

In clinical medicine, there is a suggestion that use of GCSF should be avoided, at least in children and adolescents and perhaps adults, when G-CSFR isoform IV is overexpressed.

Interactions

Granulocyte colony-stimulating factor receptor has been shown to interact with Grb2, HCK and SHC1.

See also

• Cluster of differentiation

Further reading

• 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.
• 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.
• 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. 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. 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. PMC 452996. PMID 1717255.
• Inazawa J, Fukunaga R, Seto Y, Nakagawa H, Misawa S, Abe T, Nagata S (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, Park L, Sorensen E, March CJ, Smith CA (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, Yasukawa K, Ito S, Umezawa Y (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. doi:10.1073/pnas.91.8.2985. PMC 43499. PMID 7512720.
• Dong F, Hoefsloot LH, Schelen AM, Broeders CA, Meijer Y, Veerman AJ, Touw IP, Löwenberg B (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. 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. 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. 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, Philo J (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, Rohde MF (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.

External links

• CSF3R+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)