Leukemia inhibitory factor

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Leukemia inhibitory factor (cholinergic differentiation factor)
250px PDB rendering based on 1LKI.
Available structures PDB 1emr, 1lki, 1pvh
Identifiers
Symbols	LIF; CDF; D-FACTOR; HILDA
External IDs	OMIM: 159540 MGI: 96787 HomoloGene: 1734 GeneCards: LIF Gene
Gene Ontology Molecular function • cytokine activity • leukemia inhibitory factor receptor binding • oncostatin-M receptor binding • growth factor activity Cellular component • extracellular region • extracellular space Biological process • immune response • cell surface receptor linked signal transduction • cell-cell signaling • multicellular organismal development • positive regulation of cell proliferation • tyrosine phosphorylation of Stat3 protein • muscle morphogenesis • neuron development Sources: Amigo / EGO
RNA expression pattern
250px
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3976	16878
Ensembl	ENSG00000128342	ENSMUSG00000034394
UniProt	P15018	Q3U1H5
RefSeq (mRNA)	NM_002309	NM_001039537
RefSeq (protein)	NP_002300	NP_001034626
Location (UCSC)	Chr 22: 28.97 - 28.97 Mb	Chr 11: 4.16 - 4.17 Mb
PubMed search	[1]	[2]

Leukemia inhibitory factor, or LIF, an interleukin 6 class cytokine, is a protein in cells that affects cell growth and development.

Function

LIF derives its name from its ability to induce the terminal differentiation of myeloid leukaemic cells. Other properties attributed to the cytokine include: the growth promotion and cell differentiation of different types of target cells, influence on bone metabolism, cachexia, neural development, embryogenesis and inflammation. p53 regulated LIF has been shown to facilitate implantation in the mouse model and possibly in humans.

Binding/activation

LIF binds to the specific LIF receptor (LIFR-α) which forms a heterodimer with a specific subunit common to all members of that family of receptors, the GP130 signal transducing subunit. This leads to activation of the JAK/STAT (Janus kinase/signal transducer and activator of transcription) and MAPK (mitogen activated protein kinase) cascades.

Expression

LIF is normally expressed in the trophectoderm of the developing embryo, with its receptor LIFR expressed throughout the inner cell mass. As embryonic stem cells are derived from the inner cell mass at the blastocyst stage, removing them from the inner cell mass also removes their source of LIF.

Use in stem cell culture

Removal of LIF pushes stem cells toward differentiation, but they retain their proliferative potential or pluripotency. Therefore LIF is used in mouse embryonic stem cell culture. It is necessary to maintain the stem cells in an undifferentiated state, however genetic manipulation of embryonic stem cells allows for LIF independent growth, notably overexpression of the gene Nanog.

LIF is not required for culture of human embryonic stem cells.

LIF does not work on rat ESC cultures.

Further reading

• Patterson PH (1994). "Leukemia inhibitory factor, a cytokine at the interface between neurobiology and immunology". Proc. Natl. Acad. Sci. U.S.A. 91 (17): 7833–5. doi:10.1073/pnas.91.17.7833. PMC 44497 Freely accessible. PMID 8058719. 
• Aghajanova L (2005). "Leukemia inhibitory factor and human embryo implantation". Ann. N. Y. Acad. Sci. 1034: 176–83. doi:10.1196/annals.1335.020. PMID 15731310. 
• Králícková M, Síma P, Rokyta Z (2005). "Role of the leukemia-inhibitory factor gene mutations in infertile women: the embryo-endometrial cytokine cross talk during implantation--a delicate homeostatic equilibrium". Folia Microbiol. (Praha). 50 (3): 179–86. doi:10.1007/BF02931563. PMID 16295654. CS1 maint: Multiple names: authors list (link)
• Stahl J, Gearing DP, Willson TA; et al. (1990). "Structural organization of the genes for murine and human leukemia inhibitory factor. Evolutionary conservation of coding and non-coding regions". J. Biol. Chem. 265 (15): 8833–41. PMID 1692837. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Bazan JF (1991). "Neuropoietic cytokines in the hematopoietic fold". Neuron. 7 (2): 197–208. doi:10.1016/0896-6273(91)90258-2. PMID 1714745. 
• Lowe DG, Nunes W, Bombara M; et al. (1989). "Genomic cloning and heterologous expression of human differentiation-stimulating factor". DNA. 8 (5): 351–9. PMID 2475312. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Sutherland GR, Baker E, Hyland VJ; et al. (1989). "The gene for human leukemia inhibitory factor (LIF) maps to 22q12". Leukemia. 3 (1): 9–13. PMID 2491897. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Mori M, Yamaguchi K, Abe K (1989). "Purification of a lipoprotein lipase-inhibiting protein produced by a melanoma cell line associated with cancer cachexia". Biochem. Biophys. Res. Commun. 160 (3): 1085–92. doi:10.1016/S0006-291X(89)80114-7. PMID 2730639. CS1 maint: Multiple names: authors list (link)
• Gough NM, Gearing DP, King JA; et al. (1988). "Molecular cloning and expression of the human homologue of the murine gene encoding myeloid leukemia-inhibitory factor". Proc. Natl. Acad. Sci. U.S.A. 85 (8): 2623–7. doi:10.1073/pnas.85.8.2623. PMC 280050 Freely accessible. PMID 3128791. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Williams RL, Hilton DJ, Pease S; et al. (1989). "Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells". Nature. 336 (6200): 684–7. doi:10.1038/336684a0. PMID 3143916. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Moreau JF, Donaldson DD, Bennett F; et al. (1989). "Leukaemia inhibitory factor is identical to the myeloid growth factor human interleukin for DA cells". Nature. 336 (6200): 690–2. doi:10.1038/336690a0. PMID 3143918. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Yamaguchi M, Miki N, Ono M; et al. (1995). "Inhibition of growth hormone-releasing factor production in mouse placenta by cytokines using gp130 as a signal transducer". Endocrinology. 136 (3): 1072–8. doi:10.1210/en.136.3.1072. PMID 7867561. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Schmelzer CH, Harris RJ, Butler D; et al. (1993). "Glycosylation pattern and disulfide assignments of recombinant human differentiation-stimulating factor". Arch. Biochem. Biophys. 302 (2): 484–9. doi:10.1006/abbi.1993.1243. PMID 8489250. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Aikawa J, Ikeda-Naiki S, Ohgane J; et al. (1997). "Molecular cloning of rat leukemia inhibitory factor receptor alpha-chain gene and its expression during pregnancy". Biochim. Biophys. Acta. 1353 (3): 266–76. PMID 9349722. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Hinds MG, Maurer T, Zhang JG; et al. (1998). "Solution structure of leukemia inhibitory factor". J. Biol. Chem. 273 (22): 13738–45. doi:10.1074/jbc.273.22.13738. PMID 9593715. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• "Toward a complete human genome sequence". Genome Res. 8 (11): 1097–108. 1999. PMID 9847074. 
• Tanaka M, Hara T, Copeland NG; et al. (1999). "Reconstitution of the functional mouse oncostatin M (OSM) receptor: molecular cloning of the mouse OSM receptor beta subunit". Blood. 93 (3): 804–15. PMID 9920829. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Nakashima K, Yanagisawa M, Arakawa H; et al. (1999). "Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300". Science. 284 (5413): 479–82. doi:10.1126/science.284.5413.479. PMID 10205054. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Dunham I, Shimizu N, Roe BA; et al. (1999). "The DNA sequence of human chromosome 22". Nature. 402 (6761): 489–95. doi:10.1038/990031. PMID 10591208. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)

External links

• MeSH Leukemia+Inhibitory+Factor