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Gene Review

Csf2rb  -  colony stimulating factor 2 receptor, beta...

Mus musculus

Synonyms: AI848964, AIC2B, Aic2b, Bc, CDw131, ...
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Disease relevance of Csf2rb1

  • The immune response of the beta c/IL-3 double-mutant mice to Listeria mono-cytogenes was normal, as was hematopoietic recovery after administration of the cytotoxic drug, 5-fluorouracil [1].
  • Infection of beta c mutant mice by Nippostrongylus brasiliensis resulted in the absence of blood and lung eosinophilia [2].
  • Mice lacking beta c have a low circulating eosinophil level, have impaired eosinophilic responses to parasitic infection and develop lung disease analogous to human pulmonary alveolar proteinosis (PAP) [3].
  • Here, we describe an expression defect of beta c in three of seven pediatric patients with PAP and in one patient with severe lung disease suspected to be PAP [4].
  • However, infection of cells with retrovirus encoding a more severely truncated receptor, retaining only 7 h beta c-derived extracellular residues, did not confer factor independence on these cells [5].

High impact information on Csf2rb1


Biological context of Csf2rb1


Anatomical context of Csf2rb1

  • Reconstitution of functional receptors for human granulocyte/macrophage colony-stimulating factor (GM-CSF): evidence that the protein encoded by the AIC2B cDNA is a subunit of the murine GM-CSF receptor [11].
  • Mice lacking beta c show a pulmonary alveolar proteinosis-like disease and reduced numbers of peripheral eosinophils, which are explained by the lack of GM-CSF and IL-5 function, respectively [1].
  • Mutant mIL-5R alpha, which lacks its whole cytoplasmic domain, was transfected into mouse IL-3-dependent cell line, FDC-P1 expressing AIC2B intrinsically [12].
  • Granulocyte-macrophage colony stimulating factor (GM-CSF) is a cytokine that controls the production and function of myeloid cells by interaction with a cell surface receptor composed of a specific ligand-binding alpha-chain (hGMRalpha) and a shared signal-transducing beta-chain (beta c) [13].
  • A membrane proximal domain of the human interleukin-3 receptor beta c subunit that signals DNA synthesis in NIH 3T3 cells specifically binds a complex of Src and Janus family tyrosine kinases and phosphatidylinositol 3-kinase [14].

Associations of Csf2rb1 with chemical compounds


Regulatory relationships of Csf2rb1

  • We found that the AIC2B gene was coexpressed with the AIC2A gene [10].
  • These results provide evidence that beta c tyrosines possess distinct yet overlapping functions in activating multiple signaling pathways induced by GM-CSF [16].
  • Although in vivo the artificial fusions alone are poor initiators of leukemia, p50-RARalpha readily cooperates with an activated mutant CDw131 to induce APL-like disease [17].

Other interactions of Csf2rb1

  • In contrast to the human, the mouse has two distinct but related genes, AIC2A and AIC2B, both of which are homologous to the human beta c gene [18].
  • The beta chain is the common beta chain (beta c) of receptors for IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) [8].
  • We defined two regions of IL-5R alpha for the IL-5-induced proliferative response, the expression of nuclear proto-oncogenes, and the tyrosine phosphorylation of cellular proteins including beta c, SH2/SH3-containing proteins and JAK2 kinase [19].
  • The stearated peptide blocked the binding of Lyn to the beta c receptor and the activation of Lyn [20].
  • When we analyzed signaling molecules functioning downstream of the beta-c we found that Tyr577 is essential for Shc phosphorylation, while tyrosine phosphorylation of PTP1D was mediated through Tyr577 as well as through other site(s) [21].

Analytical, diagnostic and therapeutic context of Csf2rb1


  1. Hematopoiesis in mice lacking the entire granulocyte-macrophage colony-stimulating factor/interleukin-3/interleukin-5 functions. Nishinakamura, R., Miyajima, A., Mee, P.J., Tybulewicz, V.L., Murray, R. Blood (1996) [Pubmed]
  2. Mice deficient for the IL-3/GM-CSF/IL-5 beta c receptor exhibit lung pathology and impaired immune response, while beta IL3 receptor-deficient mice are normal. Nishinakamura, R., Nakayama, N., Hirabayashi, Y., Inoue, T., Aud, D., McNeil, T., Azuma, S., Yoshida, S., Toyoda, Y., Arai, K. Immunity (1995) [Pubmed]
  3. The beta common chain (beta c) of the granulocyte macrophage-colony stimulating factor, interleukin-3 and interleukin-5 receptors. Scott, C.L., Begley, C.G. Int. J. Biochem. Cell Biol. (1999) [Pubmed]
  4. Human pulmonary alveolar proteinosis associated with a defect in GM-CSF/IL-3/IL-5 receptor common beta chain expression. Dirksen, U., Nishinakamura, R., Groneck, P., Hattenhorst, U., Nogee, L., Murray, R., Burdach, S. J. Clin. Invest. (1997) [Pubmed]
  5. Extracellular truncations of h beta c, the common signaling subunit for interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-5, lead to ligand-independent activation. D'Andrea, R.J., Barry, S.C., Moretti, P.A., Jones, K., Ellis, S., Vadas, M.A., Goodall, G.J. Blood (1996) [Pubmed]
  6. The pulmonary alveolar proteinosis in granulocyte macrophage colony-stimulating factor/interleukins 3/5 beta c receptor-deficient mice is reversed by bone marrow transplantation. Nishinakamura, R., Wiler, R., Dirksen, U., Morikawa, Y., Arai, K., Miyajima, A., Burdach, S., Murray, R. J. Exp. Med. (1996) [Pubmed]
  7. IL-5 receptor-mediated tyrosine phosphorylation of SH2/SH3-containing proteins and activation of Bruton's tyrosine and Janus 2 kinases. Sato, S., Katagiri, T., Takaki, S., Kikuchi, Y., Hitoshi, Y., Yonehara, S., Tsukada, S., Kitamura, D., Watanabe, T., Witte, O., Takatsu, K. J. Exp. Med. (1994) [Pubmed]
  8. A critical cytoplasmic domain of the interleukin-5 (IL-5) receptor alpha chain and its function in IL-5-mediated growth signal transduction. Takaki, S., Kanazawa, H., Shiiba, M., Takatsu, K. Mol. Cell. Biol. (1994) [Pubmed]
  9. 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]
  10. Cloning and expression of a gene encoding an interleukin 3 receptor-like protein: identification of another member of the cytokine receptor gene family. Gorman, D.M., Itoh, N., Kitamura, T., Schreurs, J., Yonehara, S., Yahara, I., Arai, K., Miyajima, A. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  11. Reconstitution of functional receptors for human granulocyte/macrophage colony-stimulating factor (GM-CSF): evidence that the protein encoded by the AIC2B cDNA is a subunit of the murine GM-CSF receptor. Kitamura, T., Hayashida, K., Sakamaki, K., Yokota, T., Arai, K., Miyajima, A. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  12. Reconstitution of the functional receptors for murine and human interleukin 5. Takaki, S., Murata, Y., Kitamura, T., Miyajima, A., Tominaga, A., Takatsu, K. J. Exp. Med. (1993) [Pubmed]
  13. Cytoplasmic domains of the common beta-chain of the GM-CSF/IL-3/IL-5 receptors that are required for inducing differentiation or clonal suppression in myeloid leukaemic cell lines. Smith, A., Metcalf, D., Nicola, N.A. EMBO J. (1997) [Pubmed]
  14. A membrane proximal domain of the human interleukin-3 receptor beta c subunit that signals DNA synthesis in NIH 3T3 cells specifically binds a complex of Src and Janus family tyrosine kinases and phosphatidylinositol 3-kinase. Rao, P., Mufson, R.A. J. Biol. Chem. (1995) [Pubmed]
  15. 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]
  16. Definition of the role of tyrosine residues of the common beta subunit regulating multiple signaling pathways of granulocyte-macrophage colony-stimulating factor receptor. Itoh, T., Liu, R., Yokota, T., Arai, K.I., Watanabe, S. Mol. Cell. Biol. (1998) [Pubmed]
  17. Forced retinoic acid receptor alpha homodimers prime mice for APL-like leukemia. Sternsdorf, T., Phan, V.T., Maunakea, M.L., Ocampo, C.B., Sohal, J., Silletto, A., Galimi, F., Le Beau, M.M., Evans, R.M., Kogan, S.C. Cancer Cell (2006) [Pubmed]
  18. Two distinct functional high affinity receptors for mouse interleukin-3 (IL-3). Hara, T., Miyajima, A. EMBO J. (1992) [Pubmed]
  19. Critical proline residues of the cytoplasmic domain of the IL-5 receptor alpha chain and its function in IL-5-mediated activation of JAK kinase and STAT5. Kouro, T., Kikuchi, Y., Kanazawa, H., Hirokawa, K., Harada, N., Shiiba, M., Wakao, H., Takaki, S., Takatsu, K. Int. Immunol. (1996) [Pubmed]
  20. A novel Lyn-binding peptide inhibitor blocks eosinophil differentiation, survival, and airway eosinophilic inflammation. Adachi, T., Stafford, S., Sur, S., Alam, R. J. Immunol. (1999) [Pubmed]
  21. Granulocyte-macrophage colony-stimulating factor provokes RAS activation and transcription of c-fos through different modes of signaling. Itoh, T., Muto, A., Watanabe, S., Miyajima, A., Yokota, T., Arai, K. J. Biol. Chem. (1996) [Pubmed]
  22. Enhanced expression of interleukin-3 and granulocyte-macrophage colony-stimulating factor receptor subunits in murine hematopoietic cells stimulated with hematopoietic growth factors. Liboi, E., Jubinsky, P., Andrews, N.C., Nathan, D.G., Mathey-Prevot, B. Blood (1992) [Pubmed]
  23. Mice unresponsive to GM-CSF are unexpectedly resistant to cutaneous Leishmania major infection. Scott, C.L., Roe, L., Curtis, J., Baldwin, T., Robb, L., Begley, C.G., Handman, E. Microbes Infect. (2000) [Pubmed]
  24. Collagen-induced arthritis in T cell receptor V beta congenic B10.Q mice. Nabozny, G.H., Bull, M.J., Hanson, J., Griffiths, M.M., Luthra, H.S., David, C.S. J. Exp. Med. (1994) [Pubmed]
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