The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

CSF2RA  -  colony stimulating factor 2 receptor,...

Homo sapiens

Synonyms: CD116, CDw116, CSF2R, CSF2RAX, CSF2RAY, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of CSF2RA


Psychiatry related information on CSF2RA

  • Also, schizophrenics showed negative correlations of task performance with anterior cingulate activity suggesting that overactivity of that region, which is involved in mental effort and whose GMR was low in our larger study of schizophrenia, impairs task performance in schizophrenics [5].

High impact information on CSF2RA

  • This gene, ANT3, is located approximately 1,300 kilobases from the telomere, proximal to the pseudoautosomal gene CSF2RA, and escapes X-inactivation [6].
  • The gene encoding the granulocyte macrophage colony stimulating factor receptor alpha subunit (CSF2RA) has previously been mapped to the pseudoautosomal region of the human sex chromosomes [7].
  • A high affinity IL-3-binding site (Kd = 140 +/- 30 pM) was reconstituted by coexpressing the DUK-1 protein and hGMR beta, indicating that hIL-3R and hGMR share the beta subunit [8].
  • Sequence alignment and modeling of interleukin (IL)-3R and IL-5R identified an arginine residue at the tip of a beta turn in a highly divergent context at the F'-G' loop, close to a conserved structural element, the WSXWS motif, suggesting the possibility of a ligand association mechanism similar to the one described herein for GMR [9].
  • These results indicate that the beta homodimer, which alone is insufficient for signaling, forms the functional hGMR with the alpha subunit in response to hGM-CSF [10].

Chemical compound and disease context of CSF2RA


Biological context of CSF2RA


Anatomical context of CSF2RA

  • In this paper we show that expression of the human GM-R in a heterologous cell system (primary avian erythroid and myeloid cells) confirms respective results in murine or human cell lines, but also provides new insights how the GM-R regulates progenitor proliferation and differentiation [17].
  • The GMR alpha subunit was expressed only on mature granulocytes and monocytes, and IL-3R alpha was expressed on monocytes but not on mature granulocytes, and none of these subunits were expressed on lymphocytes [18].
  • Our study showed expression levels for each receptor subunit--including GMR, IL-3R, and c-kit on human bone marrow and peripheral blood cells and leukemic cell lines--and revealed differential regulation of the expression of the receptor subunits [18].
  • The granulocyte/macrophage colony-stimulating factor (GM-CSF) receptor (GMR) transduces a signal that results in the proliferation, differentiation, and functional activation of hematopoietic cells [19].
  • Human myeloid cell lines and primary explant human lymphocytes expressing high affinity GM-CSF receptors responded to alpha GMR antibody with increased glucose uptake [20].

Associations of CSF2RA with chemical compounds

  • Only one tyrosine residue (Tyr577) existed within the region 544 to 589, and substitution of Tyr577 to phenylalanine in GMR beta 589 resulted in loss of c-fos activation [21].
  • Experiments with a construct eliminating most of the intracellular portion of alpha GMR showed a 50% reduction in GM-CSF-stimulated glucose uptake with residual activity blocked by wortmannin [20].
  • Searching for a proximally generated diffusible factor capable of activating PI 3-kinase, we identified hydrogen peroxide (H(2)O(2)), generated by ligand or antibody binding to alpha GMR, as the initiating factor [20].
  • Proliferation assays showed that the membrane-proximal conserved region of GM-R alpha and the serine-acidic domain of beta c are required for both cell proliferation and ligand-dependent phosphorylation of a 93-kD cytoplasmic protein [22].
  • As expected, solubilized membranes obtained from those cells expressing the highest number of GM-R (neutrophils and dimethyl sulfoxide-induced HL-60 cells; approximately 500-800 sites/cell) possessed the highest concentration of soluble GM-R (approximately 2-3 x 10(8) GM-R/micrograms) [23].

Physical interactions of CSF2RA

  • GMR alpha in isolation binds to GM-CSF with low affinity and can signal for increased glucose uptake [24].
  • Laminin and fibronectin binding to LR was found to prevent the binding of betaGMR to LR and relieved the LR inhibition of GMR [25].

Regulatory relationships of CSF2RA

  • GMCSF activates NF-kappaB via direct interaction of the GMCSF receptor with IkappaB kinase beta [26].
  • DTctGMCSF was selectively cytotoxic (IC50 1-10ng/ml) to GMCSF-receptor positive AML cells expressing the Pgp- or MRP-associated multi-drug resistant phenotypes, despite high level resistance to conventional chemotherapeutic agents [27].

Other interactions of CSF2RA

  • Phosphorylation of tyrosine residues in the hGMR beta subunit and several cellular proteins is observed after hGM-CSF stimulation [21].
  • Furthermore, the hGM-R alpha chain specifically interfered with EpoR signaling, an activity neither seen for the betac subunit of the receptor complex alone, nor for the alpha chain of the closely related Interleukin-3 receptor [17].
  • Much less is known, however, about GM-R function in primary hematopoietic cells [17].
  • Activation of GM-CSF receptor (GMR) triggers two distinct cytoplasmic signalling pathways, JAK2 and Ras, and is sufficient to maintain proliferation of growth factor-dependent cell lines [28].
  • Since DTctGMCSF enters and kills its target cells by unique mechanisms (GMCSF-receptor binding and protein synthesis inhibition) and is not similar in structure to Pgp or MRP substrates, we postulated that it would be an active agent against therapy-resistant AML [27].

Analytical, diagnostic and therapeutic context of CSF2RA

  • By pulsed-field gel electrophoresis, the precise localization of this gene, CSF2RA, within the pseudoautosomal region has been determined [15].
  • The present study was designed to define the assembly of the GMR complex at the molecular level through site-directed mutagenesis guided by homology modeling with the growth hormone receptor complex [9].
  • Low-affinity GMR cDNAs encoding both the membrane-bound and soluble receptors were obtained by PCR using primers corresponding to the published sequence [29].
  • Cell surface expression of GMR alpha was examined using anti-GMR alpha and flow cytometry [4].
  • Northern and reverse transcriptase-polymerase chain reaction analysis of GM-CSF-R alpha and -beta c (KH97) transcripts did not provide indications for the involvement of GM-CSF-R splice variants in the formation of the intermediate affinity GM-CSFR complex [30].


  1. Production of recombinant DTctGMCSF fusion toxin in a baculovirus expression vector system for biotherapy of GMCSF-receptor positive hematologic malignancies. Williams, M.D., Rostovtsev, A., Narla, R.K., Uckun, F.M. Protein Expr. Purif. (1998) [Pubmed]
  2. Characterization of a YAC contig spanning the pseudoautosomal region. Ried, K., Mertz, A., Nagaraja, R., Trusgnich, M., Riley, J.H., Anand, R., Lehrach, H., Page, D., Ellison, J.W., Rappold, G. Genomics (1995) [Pubmed]
  3. Granulocyte-macrophage colony-stimulating factor signals for increased glucose uptake in human melanoma cells. Spielholz, C., Heaney, M.L., Morrison, M.E., Houghton, A.N., Vera, J.C., Golde, D.W. Blood (1995) [Pubmed]
  4. Expression and function of the human granulocyte-macrophage colony-stimulating factor receptor alpha subunit. Jubinsky, P.T., Laurie, A.S., Nathan, D.G., Yetz-Aldepe, J., Sieff, C.A. Blood (1994) [Pubmed]
  5. Glucose metabolic correlates of continuous performance test performance in adults with a history of infantile autism, schizophrenics, and controls. Siegel, B.V., Nuechterlein, K.H., Abel, L., Wu, J.C., Buchsbaum, M.S. Schizophr. Res. (1995) [Pubmed]
  6. A human pseudoautosomal gene, ADP/ATP translocase, escapes X-inactivation whereas a homologue on Xq is subject to X-inactivation. Schiebel, K., Weiss, B., Wöhrle, D., Rappold, G. Nat. Genet. (1993) [Pubmed]
  7. The human pseudoautosomal GM-CSF receptor alpha subunit gene is autosomal in mouse. Disteche, C.M., Brannan, C.I., Larsen, A., Adler, D.A., Schorderet, D.F., Gearing, D., Copeland, N.G., Jenkins, N.A., Park, L.S. Nat. Genet. (1992) [Pubmed]
  8. Expression cloning of the human IL-3 receptor cDNA reveals a shared beta subunit for the human IL-3 and GM-CSF receptors. Kitamura, T., Sato, N., Arai, K., Miyajima, A. Cell (1991) [Pubmed]
  9. Crucial role of the residue R280 at the F'-G' loop of the human granulocyte/macrophage colony-stimulating factor receptor alpha chain for ligand recognition. Rajotte, D., Cadieux, C., Haman, A., Wilkes, B.C., Clark, S.C., Hercus, T., Woodcock, J.A., Lopez, A., Hoang, T. J. Exp. Med. (1997) [Pubmed]
  10. The beta subunit of human granulocyte-macrophage colony-stimulating factor receptor forms a homodimer and is activated via association with the alpha subunit. Muto, A., Watanabe, S., Miyajima, A., Yokota, T., Arai, K. J. Exp. Med. (1996) [Pubmed]
  11. Hormonal modulation of GM-CSF receptor alpha-chain in in vitro models of endometrial cancer. Baj, G., Arnulfo, A., Boldorini, R., Nicosia, G., Villa, L., Malavasi, F., Surico, N. Eur. J. Gynaecol. Oncol. (2000) [Pubmed]
  12. Gene for the alpha-subunit of the human interleukin-3 receptor (IL3RA) localized to the X-Y pseudoautosomal region. Milatovich, A., Kitamura, T., Miyajima, A., Francke, U. Am. J. Hum. Genet. (1993) [Pubmed]
  13. A cytokine receptor gene cluster in the X-Y pseudoautosomal region? Kremer, E., Baker, E., D'Andrea, R.J., Slim, R., Phillips, H., Moretti, P.A., Lopez, A.F., Petit, C., Vadas, M.A., Sutherland, G.R. Blood (1993) [Pubmed]
  14. Xp pseudoautosomal gene haploinsufficiency and linear growth deficiency in three girls with chromosome Xp22;Yq11 translocation. Joseph, M., Cantú, E.S., Pai, G.S., Willi, S.M., Papenhausen, P.R., Weiss, L. J. Med. Genet. (1996) [Pubmed]
  15. Arrangement and localization of the human GM-CSF receptor alpha chain gene CSF2RA within the X-Y pseudoautosomal region. Rappold, G., Willson, T.A., Henke, A., Gough, N.M. Genomics (1992) [Pubmed]
  16. Critical cytoplasmic domains of the common beta subunit of the human GM-CSF, IL-3 and IL-5 receptors for growth signal transduction and tyrosine phosphorylation. Sakamaki, K., Miyajima, I., Kitamura, T., Miyajima, A. EMBO J. (1992) [Pubmed]
  17. Mammalian granulocyte-macrophage colony-stimulating factor receptor expressed in primary avian hematopoietic progenitors: lineage-specific regulation of proliferation and differentiation. Wessely, O., Deiner, E.M., Lim, K.C., Mellitzer, G., Steinlein, P., Beug, H. J. Cell Biol. (1998) [Pubmed]
  18. Differential expression of granulocyte-macrophage colony-stimulating factor and IL-3 receptor subunits on human CD34+ cells and leukemic cell lines. Kurata, H., Arai, T., Yokota, T., Arai, K. J. Allergy Clin. Immunol. (1995) [Pubmed]
  19. A functional isoform of the human granulocyte/macrophage colony-stimulating factor receptor has an unusual cytoplasmic domain. Crosier, K.E., Wong, G.G., Mathey-Prevot, B., Nathan, D.G., Sieff, C.A. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  20. Granulocyte-macrophage colony-stimulating factor signals for increased glucose transport via phosphatidylinositol 3-kinase- and hydrogen peroxide-dependent mechanisms. Dhar-Mascareno, M., Chen, J., Zhang, R.H., Cárcamo, J.M., Golde, D.W. J. Biol. Chem. (2003) [Pubmed]
  21. Roles of JAK kinases in human GM-CSF receptor signal transduction. Watanabe, S., Itoh, T., Arai, K. J. Allergy Clin. Immunol. (1996) [Pubmed]
  22. Human granulocyte-macrophage colony-stimulating factor receptor signal transduction requires the proximal cytoplasmic domains of the alpha and beta subunits. Weiss, M., Yokoyama, C., Shikama, Y., Naugle, C., Druker, B., Sieff, C.A. Blood (1993) [Pubmed]
  23. Characterization of the soluble human granulocyte-macrophage colony-stimulating factor receptor complex. DiPersio, J.F., Hedvat, C., Ford, C.F., Golde, D.W., Gasson, J.C. J. Biol. Chem. (1991) [Pubmed]
  24. Membrane-associated and soluble granulocyte/macrophage-colony-stimulating factor receptor alpha subunits are independently regulated in HL-60 cells. Heaney, M.L., Vera, J.C., Raines, M.A., Golde, D.W. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  25. The laminin receptor modulates granulocyte-macrophage colony-stimulating factor receptor complex formation and modulates its signaling. Chen, J., Cárcamo, J.M., Bórquez-Ojeda, O., Erdjument-Bromage, H., Tempst, P., Golde, D.W. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  26. GMCSF activates NF-kappaB via direct interaction of the GMCSF receptor with IkappaB kinase beta. Ebner, K., Bandion, A., Binder, B.R., de Martin, R., Schmid, J.A. Blood (2003) [Pubmed]
  27. Granulocyte-macrophage colony-stimulating factor receptor-targeted therapy of chemotherapy- and radiation-resistant human myeloid leukemias. Perentesis, J.P., Bendel, A.E., Shao, Y., Warman, B., Davies, S.M., Yang, C.H., Chandan-Langlie, M., Waddick, K.G., Uckun, F.M. Leuk. Lymphoma (1997) [Pubmed]
  28. Overexpression of Shc proteins potentiates the proliferative response to the granulocyte-macrophage colony-stimulating factor and recruitment of Grb2/SoS and Grb2/p140 complexes to the beta receptor subunit. Lanfrancone, L., Pelicci, G., Brizzi, M.F., Aronica, M.G., Casciari, C., Giuli, S., Pegoraro, L., Pawson, T., Pelicci, P.G., Arouica, M.G. Oncogene (1995) [Pubmed]
  29. Identification and molecular cloning of a soluble human granulocyte-macrophage colony-stimulating factor receptor. Raines, M.A., Liu, L., Quan, S.G., Joe, V., DiPersio, J.F., Golde, D.W. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  30. Granulocyte-macrophage colony-stimulating factor receptors alter their binding characteristics during myeloid maturation through up-regulation of the affinity converting beta subunit (KH97). Budel, L.M., Hoogerbrugge, H., Pouwels, K., van Buitenen, C., Delwel, R., Löwenberg, B., Touw, I.P. J. Biol. Chem. (1993) [Pubmed]
WikiGenes - Universities