LIF_OSMleukemia inhibitory factor
|SMART accession number:||SM00080|
|Description:||OSM, Oncostatin M|
|Interpro abstract (IPR001581):|
On the basis of functional and structural similarities, the small cytokines leukemia inhibitory factor (LIF) and oncostatin (OSM) can be classified into a single family [(PUBMED:1566332), (PUBMED:1717982)].
It has been said [(PUBMED:1717982)] that LIF and OSM can be included in the IL-6 family of cytokines (IPR003573), but while all these cytokines seem to be structurally related, the sequence similarity is not high enough to allow the use of a single consensus pattern.
|GO process:||immune response (GO:0006955)|
|GO component:||extracellular region (GO:0005576)|
|GO function:||cytokine activity (GO:0005125)|
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- Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing LIF_OSM domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with LIF_OSM domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing LIF_OSM domain in the selected taxonomic class.
- Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Robinson RC et al.
- The crystal structure and biological function of leukemia inhibitory factor: implications for receptor binding.
- Cell. 1994; 77: 1101-16
- Display abstract
The structure of murine leukemia inhibitory factor (LIF) has been determined by X-ray crystallography at 2.0 A resolution. The main chain fold conforms to the four alpha-helix bundle topology previously observed for several members of the hematopoietic cytokine family. Of these, LIF shows closest structural homology to granulocyte colony-stimulating factor and growth hormone (GH). Sequence alignments for the functionally related molecules oncostatin M and ciliary neurotrophic factor, when mapped to the LIF structure, indicate regions of conserved surface character. Analysis of the biological function and receptor specificity of a series of human-mouse LIF chimeras implicate two regions of receptor interaction that are located in the fourth helix and the preceding loop. A model for receptor binding based on the structure of the GH ligand-receptor complex requires additional, novel features to account for these data.
- Hilton DJ
- LIF: lots of interesting functions.
- Trends Biochem Sci. 1992; 17: 72-6
- Display abstract
Leukaemia inhibitory factor (LIF) is one of a growing number of cytokines that cannot be readily categorized according to its functions. Rather, these pleiotropic hormones have diverse and often overlapping effects on a multitude of cell types: for example, LIF can inhibit the differentiation of embryonal stem cells on one hand and induce the differentiation of M1 leukaemic cells on the other. Recent work has shed light on the physiological effects of LIF, how these are limited, and the biochemical and biological properties of LIF and its receptor.
- Kallestad JC, Shoyab M, Linsley PS
- Disulfide bond assignment and identification of regions required for functional activity of oncostatin M.
- J Biol Chem. 1991; 266: 8940-5
- Display abstract
Oncostatin M is a polypeptide cytokine having unique structure and diverse biological activities, including the ability to inhibit growth of certain cultured tumor cells. Here we have determined the disulfide bonding pattern of recombinant oncostatin M and have used site-directed mutagenesis to identify regions of this molecule necessary for receptor binding and growth inhibitory activities. Two intramolecular disulfide bonds, C6-C127 and C49-C167, were identified in recombinant oncostatin M. Analysis of mutations at each of the five cysteines in oncostatin M indicated that mutants C49S and C167S were inactive (less than 1/10 wild type activity) in growth inhibitory assays and radioreceptor assays. Carboxyl-terminal deletion mutations terminating at S185 and beyond were active, but further shortening abolished activity in both assays. Two deletion mutants proximal to C49 (delta 22-36 and delta 44-47) and insertion mutant GAG77 also were inactive. One deletion mutant, delta 87-90, had significantly (approximately 3-fold) increased activities in both growth inhibitory assays and radioreceptor assays. A potential amphiphilic domain was identified beginning at C167 and extending toward the carboxyl terminus. Two mutants having altered hydrophobic residues within this domain (F176G and F184G) were inactive, suggesting that these residues are required for proper conformation of the receptor binding site. Taken together, these results indicate that biological activity of oncostatin M requires discontinuous regions of the molecule, including residues near the essential disulfide bond, C49-C167, and within a putative amphiphilic helix at the carboxyl terminus. Oncostatin M thus belongs to a growing family of cytokines whose interactions with their respective receptors are mediated in part by known or predicted carboxyl-terminal amphiphilic helices.
- Rose TM, Bruce AG
- Oncostatin M is a member of a cytokine family that includes leukemia-inhibitory factor, granulocyte colony-stimulating factor, and interleukin 6.
- Proc Natl Acad Sci U S A. 1991; 88: 8641-5
- Display abstract
Oncostatin M (OSM), a glycoprotein of Mr approximately 28,000 produced by activated monocyte and T-lymphocyte cell lines, was previously identified by its ability to inhibit the growth of cells from melanoma and other solid tumors. We have detected significant similarities in the primary amino acid sequences and predicted secondary structures of OSM, leukemia-inhibitory factor (LIF), granulocyte colony-stimulating factor (G-CSF), and interleukin 6 (IL-6). Analysis of the genes encoding these proteins revealed a shared exon organization, suggesting evolutionary descent from a common ancestral gene. Using a panel of DNAs from somatic cell hybrids, we have shown that OSM, like LIF, is located on human chromosome 22. We have also demonstrated that OSM has the ability to inhibit the proliferation of murine M1 myeloid leukemic cells and can induce their differentiation into macrophage-like cells, a function shared by LIF, G-CSF, and IL-6. We propose that OSM, LIF, G-CSF, and IL-6 are structurally related members of a cytokine family that have in common the ability to modulate differentiation of a variety of cell types.
- Gough NM et al.
- LIF: a molecule with divergent actions on myeloid leukaemic cells and embryonic stem cells.
- Reprod Fertil Dev. 1989; 1: 281-8
- Display abstract
We have previously characterized, purified and cloned a novel murine and human regulator [leukaemia inhibitory factor, LIF] which induces the differentiation of certain murine and human myeloid leukaemic cells. Recently we have shown that there are specific LIF receptors on murine embryonic stem [ES] and embryonal carcinoma [EC] cells and that purified recombinant LIF can substitute for feeder cells and crude sources of differentiation inhibiting activity [DIA] [such as BRL-cell-conditioned medium] in the maintenance of ES cells in a pluripotential state in vitro. Furthermore, ES cells maintained in culture in recombinant LIF for a prolonged period can give rise to germline chimaeric mice. Thus, based on a number of biochemical and biological similarities, it is likely that LIF and DIA are the same molecule. The identification of LIF as a molecule, necessary and sufficient for the maintenance of ES cells in culture, should have a profound impact on the use of these cells for genetic manipulations.
- Metabolism (metabolic pathways involving proteins which contain this domain)
% proteins involved KEGG pathway ID Description 100.00 map04060 Cytokine-cytokine receptor interaction
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with LIF_OSM domain which could be assigned to a KEGG orthologous group, and not all proteins containing LIF_OSM domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
- Structure (3D structures containing this domain)
3D Structures of LIF_OSM domains in PDB
PDB code Main view Title 1a7m LEUKAEMIA INHIBITORY FACTOR CHIMERA (MH35-LIF), NMR, 20 STRUCTURES 1emr CRYSTAL STRUCTURE OF HUMAN LEUKEMIA INHIBITORY FACTOR (LIF) 1evs CRYSTAL STRUCTURE OF HUMAN ONCOSTATIN M 1lki THE CRYSTAL STRUCTURE AND BIOLOGICAL FUNCTION OF LEUKEMIA INHIBITORY FACTOR: IMPLICATIONS FOR RECEPTOR BINDING 1pvh Crystal structure of leukemia inhibitory factor in complex with gp130 2q7n Crystal structure of Leukemia inhibitory factor in complex with LIF receptor (domains 1-5)
- Links (links to other resources describing this domain)