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Gene Review

IL3RA  -  interleukin 3 receptor, alpha (low affinity)

Homo sapiens

Synonyms: CD123, IL-3 receptor subunit alpha, IL-3R subunit alpha, IL-3R-alpha, IL-3RA, ...
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Disease relevance of IL3RA


High impact information on IL3RA

  • Expression cloning of the human IL-3 receptor cDNA reveals a shared beta subunit for the human IL-3 and GM-CSF receptors [5].
  • Therefore, it has been suggested that p210Bcr/Abl and the IL-3 receptor may activate some common signal transduction pathways [6].
  • After allergen-challenge, although no significant change in total BM CD34+ cell numbers was observed, a significant increase in the proportion of CD34+ cells expressing IL-5R alpha, but not IL-3R alpha, was detected in the 24-h post-allergen, compared with the pre-allergen bone marrow [7].
  • These results provide a correlation of the structure-function relationships of IL-3 that should prove useful in evaluating the details of IL-3-IL-3 receptor interaction and in the rational design of clinically useful derivatives of this growth factor [8].
  • Here, we show that in endothelial cells the active beta1 integrin constitutively associates with the unphosphorylated IL-3 receptor (IL-3R) beta common subunit [9].

Chemical compound and disease context of IL3RA

  • In one common type of acute myeloid leukemia, which results in maturation arrest at the myeloid precursor level, there is a mutation of FLT3, a transmembrane tyrosine kinase, which results in constitutive activation of the IL-3 receptor [10].

Biological context of IL3RA


Anatomical context of IL3RA


Associations of IL3RA with chemical compounds


Physical interactions of IL3RA

  • IL-3 could also be coimmunoprecipitated with anti-IL-3R alpha or anti-beta c MAB, but it was not covalently attached to the receptor [19].

Co-localisations of IL3RA


Regulatory relationships of IL3RA


Other interactions of IL3RA

  • Human interleukin-3 (IL-3) induces disulfide-linked IL-3 receptor alpha- and beta-chain heterodimerization, which is required for receptor activation but not high-affinity binding [19].
  • The alpha-chain of the IL-3 receptor (CD123) was detectable neither in resting HGMC nor in HGMC exposed to stem cell factor and interleukin-4 [24].
  • Incubation of CD34+ cells with TNF-alpha for 2 days significantly increased the level of beta c and G-CSF increased the number of cells with high level expression of alpha, while other factors did not affect the IL-3R expression [14].
  • Furthermore, anti c-kit antibody staining of the CD34+ fraction from CB, but not from BM, showed two intensities and the IL-3R alpha expression seemed to be higher in a fraction of low c-kit expression [14].
  • When CD38 and CD90 (Thy-1) were used for further characterization of CD34+ cells from FLV, CE increased from 37+/-23% in CD123negative to 70+/-19% in CD123negativeCD38- and from 44+/-23% in CD123low to 66+/-19% in CD123lowCD38-. No significant increase in CE or DGP progenitors was observed when CD34+ cells were sorted by CD90 and CD123 [25].

Analytical, diagnostic and therapeutic context of IL3RA


  1. A pilot study of high-dose interleukin-3 treatment of relapsed follicular small cleaved-cell lymphoma: hematologic, immunologic, and clinical results. Younes, A., Sarris, A., Consoli, U., Rodriguez, A., McLaughlin, P., Huh, Y., Starry, S., Cabanillas, F., Andreeff, M. Blood (1996) [Pubmed]
  2. Diphtheria toxin fused to human interleukin-3 is toxic to blasts from patients with myeloid leukemias. Frankel, A.E., McCubrey, J.A., Miller, M.S., Delatte, S., Ramage, J., Kiser, M., Kucera, G.L., Alexander, R.L., Beran, M., Tagge, E.P., Kreitman, R.J., Hogge, D.E. Leukemia (2000) [Pubmed]
  3. IL-3 specifically inhibits GM-CSF binding to the higher affinity receptor. Taketazu, F., Chiba, S., Shibuya, K., Kuwaki, T., Tsumura, H., Miyazono, K., Miyagawa, K., Takaku, F. J. Cell. Physiol. (1991) [Pubmed]
  4. Interleukin-3 receptor alpha chain (CD123) is widely expressed in hematologic malignancies. Muñoz, L., Nomdedéu, J.F., López, O., Carnicer, M.J., Bellido, M., Aventín, A., Brunet, S., Sierra, J. Haematologica (2001) [Pubmed]
  5. 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]
  6. Tyrosyl phosphorylation and DNA binding activity of signal transducers and activators of transcription (STAT) proteins in hematopoietic cell lines transformed by Bcr/Abl. Carlesso, N., Frank, D.A., Griffin, J.D. J. Exp. Med. (1996) [Pubmed]
  7. Allergen-induced increases in IL-5 receptor alpha-subunit expression on bone marrow-derived CD34+ cells from asthmatic subjects. A novel marker of progenitor cell commitment towards eosinophilic differentiation. Sehmi, R., Wood, L.J., Watson, R., Foley, R., Hamid, Q., O'Byrne, P.M., Denburg, J.A. J. Clin. Invest. (1997) [Pubmed]
  8. Structure-function relationships of interleukin-3. An analysis based on the function and binding characteristics of a series of interspecies chimera of gibbon and murine interleukin-3. Kaushansky, K., Shoemaker, S.G., Broudy, V.C., Lin, N.L., Matous, J.V., Alderman, E.M., Aghajanian, J.D., Szklut, P.J., VanDyke, R.E., Pearce, M.K. J. Clin. Invest. (1992) [Pubmed]
  9. {beta}1 Integrin and IL-3R coordinately regulate STAT5 activation and anchorage-dependent proliferation. Defilippi, P., Rosso, A., Dentelli, P., Calvi, C., Garbarino, G., Tarone, G., Pegoraro, L., Brizzi, M.F. J. Cell Biol. (2005) [Pubmed]
  10. Leukemia: stem cells, maturation arrest, and differentiation therapy. Sell, S. Stem cell reviews (2005) [Pubmed]
  11. 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]
  12. 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]
  13. The receptor binding site of human interleukin-3 defined by mutagenesis and molecular modeling. Klein, B.K., Feng, Y., McWherter, C.A., Hood, W.F., Paik, K., McKearn, J.P. J. Biol. Chem. (1997) [Pubmed]
  14. Expression and factor-dependent modulation of the interleukin-3 receptor subunits on human hematopoietic cells. Sato, N., Caux, C., Kitamura, T., Watanabe, Y., Arai, K., Banchereau, J., Miyajima, A. Blood (1993) [Pubmed]
  15. 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]
  16. Mutational analysis of the alpha subunit of the human interleukin-3 receptor. Rapoport, A.P., Luhowskyj, S., Doshi, P., DiPersio, J.F. Blood (1996) [Pubmed]
  17. Human IL-3 receptor signaling: rapid induction of phosphatidylcholine hydrolysis is independent of protein kinase C but dependent on tyrosine phosphorylation in transfected NIH 3T3 cells. Rao, P., Kitamura, T., Miyajima, A., Mufson, R.A. J. Immunol. (1995) [Pubmed]
  18. A novel phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase associates with the interleukin-3 receptor. Liu, L., Jefferson, A.B., Zhang, X., Norris, F.A., Majerus, P.W., Krystal, G. J. Biol. Chem. (1996) [Pubmed]
  19. Human interleukin-3 (IL-3) induces disulfide-linked IL-3 receptor alpha- and beta-chain heterodimerization, which is required for receptor activation but not high-affinity binding. Stomski, F.C., Sun, Q., Bagley, C.J., Woodcock, J., Goodall, G., Andrews, R.K., Berndt, M.C., Lopez, A.F. Mol. Cell. Biol. (1996) [Pubmed]
  20. Constitutive and induced expression of DC-SIGN on dendritic cell and macrophage subpopulations in situ and in vitro. Soilleux, E.J., Morris, L.S., Leslie, G., Chehimi, J., Luo, Q., Levroney, E., Trowsdale, J., Montaner, L.J., Doms, R.W., Weissman, D., Coleman, N., Lee, B. J. Leukoc. Biol. (2002) [Pubmed]
  21. Selective inhibition of IL-5 receptor alpha-chain gene transcription by IL-5, IL-3, and granulocyte-macrophage colony-stimulating factor in human blood eosinophils. Wang, P., Wu, P., Cheewatrakoolpong, B., Myers, J.G., Egan, R.W., Billah, M.M. J. Immunol. (1998) [Pubmed]
  22. VDUP1 upregulated by TGF-beta1 and 1,25-dihydorxyvitamin D3 inhibits tumor cell growth by blocking cell-cycle progression. Han, S.H., Jeon, J.H., Ju, H.R., Jung, U., Kim, K.Y., Yoo, H.S., Lee, Y.H., Song, K.S., Hwang, H.M., Na, Y.S., Yang, Y., Lee, K.N., Choi, I. Oncogene (2003) [Pubmed]
  23. Regulation of interleukin 3 receptor alpha chain (IL-3R alpha) on human monocytes by interleukin (IL)-4, IL-10, IL-13, and transforming growth factor beta (TGF-beta). Lévêque, C., Grafte, S., Paysant, J., Soutif, A., Lenormand, B., Vasse, M., Soria, C., Vannier, J.P. Cytokine (1998) [Pubmed]
  24. Cell surface membrane antigen phenotype of human gastrointestinal mast cells. Krauth, M.T., Majlesi, Y., Florian, S., Bohm, A., Hauswirth, A.W., Ghannadan, M., Wimazal, F., Raderer, M., Wrba, F., Valent, P. Int. Arch. Allergy Immunol. (2005) [Pubmed]
  25. Correlation between IL-3 receptor expression and growth potential of human CD34+ hematopoietic cells from different tissues. Huang, S., Chen, Z., Yu, J.F., Young, D., Bashey, A., Ho, A.D., Law, P. Stem Cells (1999) [Pubmed]
  26. Monoclonal antibody 7G3 recognizes the N-terminal domain of the human interleukin-3 (IL-3) receptor alpha-chain and functions as a specific IL-3 receptor antagonist. Sun, Q., Woodcock, J.M., Rapoport, A., Stomski, F.C., Korpelainen, E.I., Bagley, C.J., Goodall, G.J., Smith, W.B., Gamble, J.R., Vadas, M.A., Lopez, A.F. Blood (1996) [Pubmed]
  27. Efficient screening of retroviral cDNA expression libraries. Kitamura, T., Onishi, M., Kinoshita, S., Shibuya, A., Miyajima, A., Nolan, G.P. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  28. Is interleukin-3 important in antiphospholipid antibody-mediated pregnancy failure? Chamley, L.W., Konarkowska, B., Duncalf, A.M., Mitchell, M.D., Johnson, P.M. Fertil. Steril. (2001) [Pubmed]
  29. In vitro effect of stem cell factor on colony growth from acquired severe aplastic anemia. Bacigalupo, A., Piaggio, G., Podestá, M., Raffo, M.R., Tedone, E., Sogno, G., Benvenuto, F., Figari, O., Grassia, L., Bagnara, G.P. Stem Cells (1993) [Pubmed]
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