Interleukin 3

IL3
Available structures
PDB	Human UniProt search: PDBe RCSB
List of PDB id codes
	1JLI
Identifiers
Aliases	IL3, interleukin 3, IL-3, MCGF, MULTI-CSF
External IDs	OMIM: 147740; HomoloGene: 47938; GeneCards: IL3; OMA:IL3 - orthologs
Gene location (Human)
Chr.	Chromosome 5 (human)
End	132,063,204 bp
RNA expression pattern
	Top expressed in
	Achilles tendon; ; bone marrow; ; lymph node; ; appendix;
	n/a
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	growth factor activity; interleukin-3 receptor binding; cytokine activity; protein tyrosine kinase activity; interleukin-1 receptor binding;
Cellular component	extracellular region; intracellular anatomical structure; extracellular space;
Biological process	MAPK cascade; embryonic hemopoiesis; cell-cell signaling; nervous system development; positive regulation of peptidyl-tyrosine phosphorylation; immune response; peptidyl-tyrosine phosphorylation; positive regulation of tyrosine phosphorylation of STAT protein; fever generation; regulation of cytokine-mediated signaling pathway; regulation of signaling receptor activity; cytokine-mediated signaling pathway; positive regulation of cell population proliferation;
	Sources:Amigo / QuickGO
Orthologs
	3562
	n/a
	ENSG00000164399
	n/a
	P08700
	n/a
	NM_000588
	n/a
	NP_000579
	n/a
	Wikidata
View/Edit Human

Interleukin 3 (IL-3) is a protein that in humans is encoded by the IL3 gene.^[3]^[4]

Function

Interleukin 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.

Interleukin 3 stimulates the differentiation of multipotent hematopoietic stem cells into myeloid progenitor cells or, with the addition of IL-7, into lymphoid progenitor cells. In addition, 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.^[5]^[6]

Interactions

Interleukin 3 has been shown to interact with IL3RA.^[7]^[8]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000164399 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "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: 540–52. doi:10.1016/S0076-6879(85)16042-8. ISBN 978-0-12-182016-9. PMID 3003517.
^ Stomski FC, Sun Q, Bagley CJ, Woodcock J, Goodall G, Andrews RK, Berndt MC, Lopez AF (June 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.
^ Woodcock JM, Zacharakis B, Plaetinck G, Bagley CJ, Qiyu S, Hercus TR, Tavernier J, Lopez AF (November 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. 13 (21): 5176–85. PMC 395466. PMID 7957082.

Wagemaker G, Burger H, van Gils FC, van Leen RW, Wielenga JJ (1990). "Interleukin-3". Biotherapy. 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): 653–65, quiz 666. doi:10.1016/j.jaci.2003.08.015. PMID 14564341.
Mroczko B, Szmitkowski M (2004). "Hematopoietic cytokines as tumor markers". Clin. Chem. Lab. Med. 42 (12): 1347–54. 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): 1165–74. doi:10.1016/0092-8674(91)90039-2. PMID 1833064.
Urdal DL, Price V, Sassenfeld HM, Cosman D, Gillis S, Park LS (1989). "Molecular characterization of colony-stimulating factors and their receptors: human interleukin-3". Ann. N. Y. Acad. Sci. 554: 167–76. doi:10.1111/j.1749-6632.1989.tb22418.x. PMID 2544122.
Otsuka T, Miyajima A, Brown N, Otsu K, Abrams J, Saeland S, Caux C, de Waal Malefijt R, de Vries J, Meyerson P (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, Chung MP, Kovacic S, Witek-Giannotti JS, Leary AC, Kriz R, Donahue RE, Wong GG (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, Nienhuis AW, Yang YC, Clark SC, Rowley JD (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): 5913–7. doi:10.1073/pnas.84.16.5913. PMC 298973. PMID 3497400.
Dorssers L, Burger H, Bot F, Delwel R, Geurts van Kessel AH, Löwenberg B, Wagemaker G (1987). "Characterization of a human multilineage-colony-stimulating factor cDNA clone identified by a conserved noncoding sequence in mouse interleukin-3". Gene. 55 (1): 115–24. doi:10.1016/0378-1119(87)90254-X. PMID 3497843.
Chirmule N, Goonewardena H, Pahwa S, Pasieka R, Kalyanaraman VS, Pahwa S (1995). "HIV-1 envelope glycoproteins induce activation of activated protein-1 in CD4+ T cells". J. Biol. Chem. 270 (33): 19364–9. doi:10.1074/jbc.270.33.19364. PMID 7642615.{{cite journal}}: CS1 maint: unflagged free DOI (link)
Than S, Oyaizu N, Pahwa RN, Kalyanaraman VS, Pahwa S (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, Stock W, Roulston D, Larson RA, Keinanen M, Westbrook CA (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): 5484–8. doi:10.1073/pnas.90.12.5484. PMC 46745. PMID 8516290.
Stomski FC, Sun Q, Bagley CJ, Woodcock J, Goodall G, Andrews RK, Berndt MC, Lopez AF (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): 524–41. doi:10.1006/jmbi.1996.0337. PMID 8676386.
Vanhaesebroeck B, Welham MJ, Kotani K, Stein R, Warne PH, Zvelebil MJ, Higashi K, Volinia S, Downward J, Waterfield MD (1997). "P110delta, a novel phosphoinositide 3-kinase in leukocytes". Proc. Natl. Acad. Sci. U.S.A. 94 (9): 4330–5. doi:10.1073/pnas.94.9.4330. PMC 20722. PMID 9113989.
Klein BK, Feng Y, McWherter CA, Hood WF, Paik K, McKearn JP (1997). "The receptor binding site of human interleukin-3 defined by mutagenesis and molecular modeling". J. Biol. Chem. 272 (36): 22630–41. doi:10.1074/jbc.272.36.22630. PMID 9278420.{{cite journal}}: CS1 maint: unflagged free DOI (link)
Sanchez X, Suetomi K, Cousins-Hodges B, Horton JK, Navarro J (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, Shirabe T, Konishi Y (1998). "Interleukin-3 and interleukin-3 receptors in the brain". Ann. N. Y. Acad. Sci. 840: 107–16. doi:10.1111/j.1749-6632.1998.tb09554.x. PMID 9629242.
Nilsen EM, Johansen FE, Jahnsen FL, Lundin KE, Scholz T, Brandtzaeg P, Haraldsen G (1998). "Cytokine profiles of cultured microvascular endothelial cells from the human intestine". Gut. 42 (5): 635–42. doi:10.1136/gut.42.5.635. PMC 1727090. PMID 9659156.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000164399 – Ensembl, May 2017

[2] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-3] "Entrez Gene: IL3 interleukin 3 (colony-stimulating factor, multiple)".

[pmid3489530-4] 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.

[pmid6971890-5] 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.

[pmid3003517-6] Ihle JN, Weinstein Y, Keller J, Henderson L, Palaszynski E (1985). "Interleukin 3". Meth. Enzymol. Methods in Enzymology. 116: 540–52. doi:10.1016/S0076-6879(85)16042-8. ISBN 978-0-12-182016-9. PMID 3003517.

[pmid8649415-7] Stomski FC, Sun Q, Bagley CJ, Woodcock J, Goodall G, Andrews RK, Berndt MC, Lopez AF (June 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.

[pmid7957082-8] Woodcock JM, Zacharakis B, Plaetinck G, Bagley CJ, Qiyu S, Hercus TR, Tavernier J, Lopez AF (November 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. 13 (21): 5176–85. PMC 395466. PMID 7957082.

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[2]

[3]

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[5]

[6]

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[8]

v t e Colony-stimulating factors
CFU-GEMM	Interleukin 3
CFU-GM	Granulocyte macrophage colony-stimulating factor Granulocyte colony-stimulating factor Macrophage colony-stimulating factor
CFU-E	Erythropoietin
CFU-Meg	Thrombopoietin

Interleukin 3

Function

Discovery

Interactions

See also

References

Further reading