Interleukin 3
Interleukin 3, also known as IL-3, is a protein that in humans is encoded by the IL3 gene.[1][2]
Function
Interleukin-3 (IL-3) is an interleukin, a type of biological signal (cytokine) that can improve the body's natural response to disease as part of the immune system. It acts by binding to the interleukin-3 receptor.
IL-3 stimulates the differentiation of multipotent hematopoietic stem cells into myeloid progenitor cells or, with the addition of IL-7, into lymphoid progenitor cells. Additionally, IL-3 stimulates proliferation of all cells in the myeloid lineage (granulocytes, monocytes, and dendritic cells), in conjunction with other cytokines, e.g., Erythropoietin (EPO), Granulocyte macrophage colony-stimulating factor (GM-CSF), and IL-6. It is secreted by basophils and activated T cells to support growth and differentiation of T cells from the bone marrow in an immune response. Activated T cells can either induce their own proliferation and differentiation (autocrine signalling), or that of other T cells (paracrine signalling) - both involve IL-2 binding to the IL-2 receptor on T cells (upregulated upon cell activation, under the induction of macrophage-secreted IL-1). The human IL-3 gene encodes a protein 152 amino acids long, and the naturally occurring IL-3 is glycosylated. The human IL-3 gene is located on chromosome 5, only 9 kilobases from the GM-CSF gene, and its function is quite similar to GM-CSF.
Discovery
Interleukin-3 originally was discovered by JN Ihle in mice. He found a T cell derived factor that induced the synthesis of 20alpha-hydroxysteroid dehydrogenase in hematopoietic cells and termed it interleukin-3.[3][4]
References
- ^ "Entrez Gene: IL3 interleukin 3 (colony-stimulating factor, multiple)".
- ^ Yang YC, Ciarletta AB, Temple PA, Chung MP, Kovacic S, Witek-Giannotti JS, Leary AC, Kriz R, Donahue RE, Wong GG (October 1986). "Human IL-3 (multi-CSF): identification by expression cloning of a novel hematopoietic growth factor related to murine IL-3". Cell 47 (1): 3–10. doi:10.1016/0092-8674(86)90360-0. PMID 3489530.
- ^ Ihle JN, Pepersack L, Rebar L (June 1981). "Regulation of T cell differentiation: in vitro induction of 20 alpha-hydroxysteroid dehydrogenase in splenic lymphocytes from athymic mice by a unique lymphokine". J. Immunol. 126 (6): 2184–9. PMID 6971890.
- ^ Ihle JN, Weinstein Y, Keller J, Henderson L, Palaszynski E (1985). "Interleukin 3". Meth. Enzymol. Methods in Enzymology 116: 540–552. doi:10.1016/S0076-6879(85)16042-8. ISBN 978-0-12-182016-9. PMID 3003517.
- ^ Stomski, F C; Sun Q, Bagley C J, Woodcock J, Goodall G, Andrews R K, Berndt M C, Lopez A F (Jun. 1996). "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". Mol. Cell. Biol. (UNITED STATES) 16 (6): 3035–46. ISSN 0270-7306. PMC 231298. PMID 8649415.
- ^ Woodcock, J M; Zacharakis B, Plaetinck G, Bagley C J, Qiyu S, Hercus T R, Tavernier J, Lopez A F (Nov. 1994). "Three residues in the common beta chain of the human GM-CSF, IL-3 and IL-5 receptors are essential for GM-CSF and IL-5 but not IL-3 high affinity binding and interact with Glu21 of GM-CSF". EMBO J. (ENGLAND) 13 (21): 5176–85. ISSN 0261-4189. PMC 395466. PMID 7957082.
Further reading
- Wagemaker G, Burger H, van Gils FC et al. (1991). "Interleukin-3". Biotherapy (Dordrecht, Netherlands) 2 (4): 337–45. doi:10.1007/BF02170083. PMID 2268499.
- Martinez-Moczygemba M, Huston DP (2003). "Biology of common beta receptor-signaling cytokines: IL-3, IL-5, and GM-CSF". J. Allergy Clin. Immunol. 112 (4): 653–665. doi:10.1016/j.jaci.2003.08.015. PMID 14564341.
- Mroczko B, Szmitkowski M (2005). "Hematopoietic cytokines as tumor markers". Clin. Chem. Lab. Med. 42 (12): 1347–1354. doi:10.1515/CCLM.2004.253. PMID 15576295.
- Kitamura T, Sato N, Arai K, Miyajima A (1991). "Expression cloning of the human IL-3 receptor cDNA reveals a shared beta subunit for the human IL-3 and GM-CSF receptors". Cell 66 (6): 1165–1174. doi:10.1016/0092-8674(91)90039-2. PMID 1833064.
- Urdal DL, Price V, Sassenfeld HM et al. (1989). "Molecular characterization of colony-stimulating factors and their receptors: human interleukin-3". Ann. N. Y. Acad. Sci. 554: 167–176. doi:10.1111/j.1749-6632.1989.tb22418.x. PMID 2544122.
- Otsuka T, Miyajima A, Brown N et al. (1988). "Isolation and characterization of an expressible cDNA encoding human IL-3. Induction of IL-3 mRNA in human T cell clones". J. Immunol. 140 (7): 2288–95. PMID 3127463.
- Yang YC, Ciarletta AB, Temple PA et al. (1986). "Human IL-3 (multi-CSF): identification by expression cloning of a novel hematopoietic growth factor related to murine IL-3". Cell 47 (1): 3–10. doi:10.1016/0092-8674(86)90360-0. PMID 3489530.
- Le Beau MM, Epstein ND, O'Brien SJ et al. (1987). "The interleukin 3 gene is located on human chromosome 5 and is deleted in myeloid leukemias with a deletion of 5q". Proc. Natl. Acad. Sci. U.S.A. 84 (16): 5913–5917. doi:10.1073/pnas.84.16.5913. PMC 298973. PMID 3497400.
- Dorssers L, Burger H, Bot F et al. (1987). "Characterization of a human multilineage-colony-stimulating factor cDNA clone identified by a conserved noncoding sequence in mouse interleukin-3". Gene 55 (1): 115–124. doi:10.1016/0378-1119(87)90254-X. PMID 3497843.
- Chirmule N, Goonewardena H, Pahwa S et al. (1995). "HIV-1 envelope glycoproteins induce activation of activated protein-1 in CD4+ T cells". J. Biol. Chem. 270 (33): 19364–19369. doi:10.1074/jbc.270.33.19364. PMID 7642615.
- Than S, Oyaizu N, Pahwa RN et al. (1994). "Effect of human immunodeficiency virus type-1 envelope glycoprotein gp160 on cytokine production from cord-blood T cells". Blood 84 (1): 184–8. PMID 8018916.
- Le Beau MM, Espinosa R, Neuman WL et al. (1993). "Cytogenetic and molecular delineation of the smallest commonly deleted region of chromosome 5 in malignant myeloid diseases". Proc. Natl. Acad. Sci. U.S.A. 90 (12): 5484–5488. doi:10.1073/pnas.90.12.5484. PMC 46745. PMID 8516290.
- Stomski FC, Sun Q, Bagley CJ et al. (1996). "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". Mol. Cell. Biol. 16 (6): 3035–46. PMC 231298. PMID 8649415.
- Feng Y, Klein BK, McWherter CA (1996). "Three-dimensional solution structure and backbone dynamics of a variant of human interleukin-3". J. Mol. Biol. 259 (3): 524–541. doi:10.1006/jmbi.1996.0337. PMID 8676386.
- Vanhaesebroeck B, Welham MJ, Kotani K et al. (1997). "P110delta, a novel phosphoinositide 3-kinase in leukocytes". Proc. Natl. Acad. Sci. U.S.A. 94 (9): 4330–4335. doi:10.1073/pnas.94.9.4330. PMC 20722. PMID 9113989.
- Klein BK, Feng Y, McWherter CA et al. (1997). "The receptor binding site of human interleukin-3 defined by mutagenesis and molecular modeling". J. Biol. Chem. 272 (36): 22630–22641. doi:10.1074/jbc.272.36.22630. PMID 9278420.
- Sanchez X, Suetomi K, Cousins-Hodges B et al. (1998). "CXC chemokines suppress proliferation of myeloid progenitor cells by activation of the CXC chemokine receptor 2". J. Immunol. 160 (2): 906–10. PMID 9551928.
- Tabira T, Chui DH, Fan JP et al. (1998). "Interleukin-3 and interleukin-3 receptors in the brain". Ann. N. Y. Acad. Sci. 840: 107–116. doi:10.1111/j.1749-6632.1998.tb09554.x. PMID 9629242.
- Nilsen EM, Johansen FE, Jahnsen FL et al. (1998). "Cytokine profiles of cultured microvascular endothelial cells from the human intestine". Gut 42 (5): 635–642. doi:10.1136/gut.42.5.635. PMC 1727090. PMID 9659156.
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