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Gene Review

Il3  -  interleukin 3

Mus musculus

Synonyms: BPA, Csfmu, HCGF, Hematopoietic growth factor, IL-3, ...
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Disease relevance of Il3


Psychiatry related information on Il3

  • Through the production of these cytokines with IL 3-like capacity keratinocytes may participate in the regulation of the activity of different hematopoietic cells and thereby turn on early nonspecific host defense mechanisms against transformed cells and various harmful microbial organisms [6].
  • Upon injection of v-H-ras-expressing, transformation-competent cells into mice, the final, fully malignant phenotype developed with a long latency period and was marked in vitro by independence of exogenous IL-3 and by autocrine IL-3 stimulation [7].

High impact information on Il3

  • The panspecific hemopoietin of activated T lymphocytes (interleukin-3) [8].
  • The lipocalin mouse 24p3 has been implicated in diverse physiological processes, including apoptosis due to interleukin-3 (IL-3) deprivation and iron transport [9].
  • Transfection of the human bcl-2 gene into an interleukin-3 (IL-3)-dependent, multipotent hemopoietic cell line allowed these cells to survive in the absence of IL-3, both in serum-containing and serum-deprived conditions, and this survival was accompanied by multilineage differentiation [10].
  • Stimulation via cytokine receptors such as IL-2 and IL-3 receptors, but not by the EGF receptor (EGFR), induces cells of the BAF-B03 hematopoietic cell line to transit the cell cycle [11].
  • Our data indicate that activation of the GM-CSF receptor induces differentiation of stem cells by an instructive mechanism that can be blocked by the activated IL-3 receptor [12].

Chemical compound and disease context of Il3


Biological context of Il3


Anatomical context of Il3

  • BSF-1 activity, including the ability to enhance the growth of IL-3-dependent mast cells, was detected in the supernatants of transformed mast cells [22].
  • Fibroblasts transfected with the complementary DNA bound IL-3 with a low affinity [dissociation constant (Kd) of 17.9 +/- 3.6 nM] [18].
  • These cells represent the first nontransformed cell lines which can be maintained in growth factors other than IL-3 and which differentiate in the presence of physiologic signals [23].
  • The two murine haemopoietic growth factors, granulocyte-macrophage colony stimulating factor (GM-CSF) and Multi-CSF (interleukin 3) stimulate the proliferation and differentiation of an overlapping set of haemopoietic progenitor cells and are produced coordinately following activation of T lymphocytes [24].
  • Both high affinity IL-3Rs expressed on a mouse T cell line, CTLL-2, showed similar IL-3 binding properties and transmitted a growth signal in response to IL-3 [25].

Associations of Il3 with chemical compounds

  • It is well established that murine multipotential and committed erythroid progenitor cells require the presence of a glycoprotein, termed multi-CSF (multi-colony-stimulating factor, IL-3) for clonal proliferation and differentiation in vitro [26].
  • Mouse bone marrow-derived mast cells (BMMCs) developed with interleukin 3 (IL-3) can be stimulated by c-kit ligand (KL) and accessory cytokines over a period of hours for direct delayed prostaglandin (PG) generation or over a period of days to prime for augmented IgE-dependent PG and leukotriene (LT) production, as previously reported [27].
  • IL-4 inhibited the priming for increased IgE-dependent PGD2 and LTC4 production to the level obtained by activation of BMMCs maintained in IL-3 alone with an IC50 of approximately 0.2 ng/ml [27].
  • First, we tested the effects of IL-3 on lymphohematopoietic progenitors by using lineage-negative (Lin-) marrow cells of 5-fluorouracil (5-FU)-treated mice in the two-step methylcellulose culture we reported previously [28].
  • Maximal levels of pro-B cell expansion, generally resulting in 15- to 30-fold increases in cellularity, were obtained in cultures supplemented with optimal doses of FL + IL-7 + IL-3 [29].

Physical interactions of Il3


Enzymatic interactions of Il3

  • Cross-linking of CD16/Jak2 stimulates the tyrosine phosphorylation of a large group of proteins that are also phosphorylated after the addition of IL-3 or GM-CSF and include proteins of 145, 97, 67, 52, and 42 kDa [35].
  • Active, but not inactive, forms of Akt were found to phosphorylate BAD in vivo and in vitro at the same residues that are phosphorylated in response to IL-3 [36].
  • We could reveal that the C-terminal half of the Tec N-terminal unique domain (NTec2 region) can bind to a set of tyrosine-phosphorylated cellular proteins in vitro in an IL-3-dependent manner [37].
  • Among the NTec2-bound Lyn proteins, only the p56 form seems to be inducibly tyrosine-phosphorylated in response to IL-3 [37].

Regulatory relationships of Il3


Other interactions of Il3


Analytical, diagnostic and therapeutic context of Il3


  1. Differentiation state and responses to hematopoietic growth factors of murine myeloid cells transformed by myb. Gonda, T.J., Macmillan, E.M., Townsend, P.V., Hapel, A.J. Blood (1993) [Pubmed]
  2. Hematopoietic cytokines inhibit apoptosis induced by transforming growth factor beta 1 and cancer chemotherapy compounds in myeloid leukemic cells. Lotem, J., Sachs, L. Blood (1992) [Pubmed]
  3. Expression of the interleukin-3 and granulocyte-macrophage colony-stimulating factor genes in Friend spleen focus-forming virus-induced erythroleukemia. Shimada, Y., Migliaccio, G., Ruscetti, S., Adamson, J.W., Migliaccio, A.R. Blood (1992) [Pubmed]
  4. Primitive interleukin 3 null hematopoietic cells transduced with BCR-ABL show accelerated loss after culture of factor-independence in vitro and leukemogenic activity in vivo. Jiang, X., Ng, E., Yip, C., Eisterer, W., Chalandon, Y., Stuible, M., Eaves, A., Eaves, C.J. Blood (2002) [Pubmed]
  5. 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]
  6. Keratinocyte-derived interleukin 3. Luger, T.A., Kock, A., Kirnbauer, R., Schwarz, T., Ansel, J.C. Ann. N. Y. Acad. Sci. (1988) [Pubmed]
  7. A v-H-ras-dependent hemopoietic tumor model involving progression from a clonal stage of transformation competence to autocrine interleukin 3 production. Nair, A.P., Diamantis, I.D., Conscience, J.F., Kindler, V., Hofer, P., Moroni, C. Mol. Cell. Biol. (1989) [Pubmed]
  8. The panspecific hemopoietin of activated T lymphocytes (interleukin-3). Schrader, J.W. Annu. Rev. Immunol. (1986) [Pubmed]
  9. A cell-surface receptor for lipocalin 24p3 selectively mediates apoptosis and iron uptake. Devireddy, L.R., Gazin, C., Zhu, X., Green, M.R. Cell (2005) [Pubmed]
  10. Suppression of apoptosis allows differentiation and development of a multipotent hemopoietic cell line in the absence of added growth factors. Fairbairn, L.J., Cowling, G.J., Reipert, B.M., Dexter, T.M. Cell (1993) [Pubmed]
  11. IL-2 and EGF receptors stimulate the hematopoietic cell cycle via different signaling pathways: demonstration of a novel role for c-myc. Shibuya, H., Yoneyama, M., Ninomiya-Tsuji, J., Matsumoto, K., Taniguchi, T. Cell (1992) [Pubmed]
  12. Expression of the GM-CSF gene after retroviral transfer in hematopoietic stem cell lines induces synchronous granulocyte-macrophage differentiation. Just, U., Stocking, C., Spooncer, E., Dexter, T.M., Ostertag, W. Cell (1991) [Pubmed]
  13. Interleukin-3 enhances cytokine production by LPS-stimulated macrophages. Cohen, L., David, B., Cavaillon, J.M. Immunol. Lett. (1991) [Pubmed]
  14. In-vivo effect of interleukin 3 and erythropoietin, either alone or in combination, on the hematopoietic toxicity associated with zidovudine. Gallicchio, V.S., Hughes, N.K., Tse, K.F. Cytokine (1993) [Pubmed]
  15. Signal transducer and activator of transcription (STAT)5 activation by BCR/ABL is dependent on intact Src homology (SH)3 and SH2 domains of BCR/ABL and is required for leukemogenesis. Nieborowska-Skorska, M., Wasik, M.A., Slupianek, A., Salomoni, P., Kitamura, T., Calabretta, B., Skorski, T. J. Exp. Med. (1999) [Pubmed]
  16. The v-fms oncogene induces factor-independent growth and transformation of the interleukin-3-dependent myeloid cell line FDC-P1. Wheeler, E.F., Askew, D., May, S., Ihle, J.N., Sherr, C.J. Mol. Cell. Biol. (1987) [Pubmed]
  17. Effector function for RAS oncogene in interleukin-3-dependent myeloid cells involves diminished efficacy of prostaglandin E1-mediated inhibition of proliferation. Derigs, H.G., Klingberg, D., Tricot, G.J., Boswell, H.S. Blood (1989) [Pubmed]
  18. Cloning of an interleukin-3 receptor gene: a member of a distinct receptor gene family. Itoh, N., Yonehara, S., Schreurs, J., Gorman, D.M., Maruyama, K., Ishii, A., Yahara, I., Arai, K., Miyajima, A. Science (1990) [Pubmed]
  19. Hematopoietic development of embryonic stem cells in vitro: cytokine and receptor gene expression. Schmitt, R.M., Bruyns, E., Snodgrass, H.R. Genes Dev. (1991) [Pubmed]
  20. Transforming growth factor beta 1 is an inducer of erythroid differentiation. Krystal, G., Lam, V., Dragowska, W., Takahashi, C., Appel, J., Gontier, A., Jenkins, A., Lam, H., Quon, L., Lansdorp, P. J. Exp. Med. (1994) [Pubmed]
  21. Comparative effects in vivo of recombinant murine interleukin 3, natural murine colony-stimulating factor-1, and recombinant murine granulocyte-macrophage colony-stimulating factor on myelopoiesis in mice. Broxmeyer, H.E., Williams, D.E., Cooper, S., Shadduck, R.K., Gillis, S., Waheed, A., Urdal, D.L., Bicknell, D.C. J. Clin. Invest. (1987) [Pubmed]
  22. B cell stimulatory factor-1/interleukin-4 mRNA is expressed by normal and transformed mast cells. Brown, M.A., Pierce, J.H., Watson, C.J., Falco, J., Ihle, J.N., Paul, W.E. Cell (1987) [Pubmed]
  23. Selection of lineage-restricted cell lines immortalized at different stages of hematopoietic differentiation from the murine cell line 32D. Migliaccio, G., Migliaccio, A.R., Kreider, B.L., Rovera, G., Adamson, J.W. J. Cell Biol. (1989) [Pubmed]
  24. Close genetic and physical linkage between the murine haemopoietic growth factor genes GM-CSF and Multi-CSF (IL3). Barlow, D.P., Bućan, M., Lehrach, H., Hogan, B.L., Gough, N.M. EMBO J. (1987) [Pubmed]
  25. Two distinct functional high affinity receptors for mouse interleukin-3 (IL-3). Hara, T., Miyajima, A. EMBO J. (1992) [Pubmed]
  26. Stimulation of multipotential, erythroid and other murine haematopoietic progenitor cells by adherent cell lines in the absence of detectable multi-CSF (IL-3). Li, C.L., Johnson, G.R. Nature (1985) [Pubmed]
  27. Interleukin 4 suppresses c-kit ligand-induced expression of cytosolic phospholipase A2 and prostaglandin endoperoxide synthase 2 and their roles in separate pathways of eicosanoid synthesis in mouse bone marrow-derived mast cells. Murakami, M., Penrose, J.F., Urade, Y., Austen, K.F., Arm, J.P. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  28. Negative regulation by interleukin-3 (IL-3) of mouse early B-cell progenitors and stem cells in culture: transduction of the negative signals by betac and betaIL-3 proteins of IL-3 receptor and absence of negative regulation by granulocyte-macrophage colony-stimulating factor. Matsunaga, T., Hirayama, F., Yonemura, Y., Murray, R., Ogawa, M. Blood (1998) [Pubmed]
  29. The FLK2/FLT3 ligand synergizes with interleukin-7 in promoting stromal-cell-independent expansion and differentiation of human fetal pro-B cells in vitro. Namikawa, R., Muench, M.O., de Vries, J.E., Roncarolo, M.G. Blood (1996) [Pubmed]
  30. Activation of 70-kDa S6 kinase, induced by the cytokines interleukin-3 and erythropoietin and inhibited by rapamycin, is not an absolute requirement for cell proliferation. Calvo, V., Wood, M., Gjertson, C., Vik, T., Bierer, B.E. Eur. J. Immunol. (1994) [Pubmed]
  31. Stem cell factor activates STAT-5 DNA binding in IL-3-derived bone marrow mast cells. Ryan, J.J., Huang, H., McReynolds, L.J., Shelburne, C., Hu-Li, J., Huff, T.F., Paul, W.E. Exp. Hematol. (1997) [Pubmed]
  32. Expression of IL-3 receptor in testis. Morikawa, Y., Tohya, K., Hara, T., Kitamura, T., Miyajima, A. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  33. Infection with Nippostrongylus brasiliensis or injection of anti-IgD antibodies markedly enhances Fc-receptor-mediated interleukin 4 production by non-B, non-T cells. Conrad, D.H., Ben-Sasson, S.Z., Le Gros, G., Finkelman, F.D., Paul, W.E. J. Exp. Med. (1990) [Pubmed]
  34. P210 Bcr-Abl interacts with the interleukin 3 receptor beta(c) subunit and constitutively induces its tyrosine phosphorylation. Wilson-Rawls, J., Xie, S., Liu, J., Laneuville, P., Arlinghaus, R.B. Cancer Res. (1996) [Pubmed]
  35. Signal transduction by a CD16/CD7/Jak2 fusion protein. Sakai, I., Nabell, L., Kraft, A.S. J. Biol. Chem. (1995) [Pubmed]
  36. Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. del Peso, L., González-García, M., Page, C., Herrera, R., Nuñez, G. Science (1997) [Pubmed]
  37. Tec protein-tyrosine kinase directly associates with Lyn protein-tyrosine kinase through its N-terminal unique domain. Mano, H., Sato, K., Yazaki, Y., Hirai, H. Oncogene (1994) [Pubmed]
  38. Interleukin-3 signals through multiple isoforms of Stat5. Azam, M., Erdjument-Bromage, H., Kreider, B.L., Xia, M., Quelle, F., Basu, R., Saris, C., Tempst, P., Ihle, J.N., Schindler, C. EMBO J. (1995) [Pubmed]
  39. Interferon-gamma stimulates the survival and influences the development of bipotential granulocyte-macrophage colony-forming cells. Kan, O., Heyworth, C.M., Dexter, T.M., Maudsley, P.J., Cook, N., Vallance, S.J., Whetton, A.D. Blood (1991) [Pubmed]
  40. Erythropoietin receptor haploinsufficiency and in vivo interplay with granulocyte-macrophage colony-stimulating factor and interleukin 3. Jegalian, A.G., Acurio, A., Dranoff, G., Wu, H. Blood (2002) [Pubmed]
  41. Megakaryocyte growth and development factor and interleukin-3 induce patterns of protein-tyrosine phosphorylation that correlate with dominant differentiation over proliferation of mpl-transfected 32D cells. Mu, S.X., Xia, M., Elliott, G., Bogenberger, J., Swift, S., Bennett, L., Lappinga, D.L., Hecht, R., Lee, R., Saris, C.J. Blood (1995) [Pubmed]
  42. Characterization of antigen-specific CD4+ effector T cells in vivo: immunization results in a transient population of MEL-14-, CD45RB- helper cells that secretes interleukin 2 (IL-2), IL-3, IL-4, and interferon gamma. Bradley, L.M., Duncan, D.D., Tonkonogy, S., Swain, S.L. J. Exp. Med. (1991) [Pubmed]
  43. Interleukin 6 enhancement of interleukin 3-dependent proliferation of multipotential hemopoietic progenitors. Ikebuchi, K., Wong, G.G., Clark, S.C., Ihle, J.N., Hirai, Y., Ogawa, M. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  44. Pluripotent hematopoietic stem cells contain high levels of mRNA for c-kit, GATA-2, p45 NF-E2, and c-myb and low levels or no mRNA for c-fms and the receptors for granulocyte colony-stimulating factor and interleukins 5 and 7. Orlic, D., Anderson, S., Biesecker, L.G., Sorrentino, B.P., Bodine, D.M. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  45. Rel-deficient T cells exhibit defects in production of interleukin 3 and granulocyte-macrophage colony-stimulating factor. Gerondakis, S., Strasser, A., Metcalf, D., Grigoriadis, G., Scheerlinck, J.Y., Grumont, R.J. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  46. Identification of 24p3 as a direct target of Foxo3a regulated by interleukin-3 through the phosphoinositide 3-kinase/Akt pathway. Park, S., Guo, J., Kim, D., Cheng, J.Q. J. Biol. Chem. (2009) [Pubmed]
  47. Murine pluripotent hematopoietic progenitors constitutively expressing a normal erythropoietin receptor proliferate in response to erythropoietin without preferential erythroid cell differentiation. Dubart, A., Feger, F., Lacout, C., Goncalves, F., Vainchenker, W., Dumenil, D. Mol. Cell. Biol. (1994) [Pubmed]
  48. A soluble activity from adherent marrow cells cooperates with IL 3 in stimulating growth of pluripotential hematopoietic precursors. Iscove, N.N., Fagg, B., Keller, G. Blood (1988) [Pubmed]
  49. Biologic significance of constitutive and subliminal growth factor production by bone marrow stroma. Kittler, E.L., McGrath, H., Temeles, D., Crittenden, R.B., Kister, V.K., Quesenberry, P.J. Blood (1992) [Pubmed]
  50. Apoptosis and hematopoiesis in murine fetal liver. Yu, H., Bauer, B., Lipke, G.K., Phillips, R.L., Van Zant, G. Blood (1993) [Pubmed]
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