Biology:Granulocyte colony-stimulating factor receptor

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

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.[1] G-CSF-R is a cell-surface receptor for the granulocyte colony-stimulating factor (G-CSF).[2] The G-CSF receptors belong 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,[3] and colony-stimulating.

Clinical significance

Mutations in this gene are a cause of Kostmann syndrome, also known as severe congenital neutropenia.[4]

Mutations in the intracellular part of this receptor are also associated with certain types of leukemia.[5]

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.[6]

Interactions

Granulocyte colony-stimulating factor receptor has been shown to interact with Grb2,[7] HCK[8] and SHC1.[7]

See also

References

  1. ↑ "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. March 1992. doi:10.1182/blood.V79.5.1148.1148. PMID 1371413. 
  2. ↑ "Entrez Gene: CSF3R colony stimulating factor 3 receptor (granulocyte)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1441. 
  3. ↑ Mehta, H M; Futami, M; Glaubach, T; Lee, D W; Andolina, J R; Yang, Q; Whichard, Z; Quinn, M 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. ISSN 1476-5551. PMID 24170028. 
  4. ↑ "Kostmann syndrome and severe congenital neutropenia". Semin. Hematol. 39 (2): 82–8. April 2002. doi:10.1053/shem.2002.31913. PMID 11957189. 
  5. ↑ "G-CSF and its receptor in myeloid malignancy". Blood 115 (25): 5131–6. June 2010. doi:10.1182/blood-2010-01-234120. PMID 20237318. 
  6. ↑ "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. May 2010. doi:10.1200/JCO.2009.25.9010. PMID 20406937. 
  7. ↑ 7.0 7.1 "Direct binding of Shc, Grb2, SHP-2 and p40 to the murine granulocyte colony-stimulating factor receptor". Biochim. Biophys. Acta 1448 (1): 70–6. November 1998. doi:10.1016/S0167-4889(98)00120-7. PMID 9824671. 
  8. ↑ "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. October 1998. doi:10.1006/bbrc.1998.9441. PMID 9790917. 

Further reading

External links



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