Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/28022
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dc.contributor.authorHaines, Bryan Peteren
dc.contributor.authorVoyle, Roger Bruceen
dc.contributor.authorRathjen, Peter Daviden
dc.date.issued2000en
dc.identifier.citationMolecular Biology of the Cell, 2000; 11(4):1369-1383en
dc.identifier.issn1059-1524en
dc.identifier.urihttp://hdl.handle.net/2440/28022-
dc.description.abstractAlthough many growth factors and cytokines have been shown to be localized within the cell and nucleus, the mechanism by which these molecules elicit a biological response is not well understood. The cytokine leukemia inhibitory factor (LIF) provides a tractable experimental system to investigate this problem, because translation of alternatively spliced transcripts results in the production of differentially localized LIF proteins, one secreted from the cell and acting via cell surface receptors and the other localized within the cell. We have used overexpression analysis to demonstrate that extracellular and intracellular LIF proteins can have distinct cellular activities. Intracellular LIF protein is localized to both nucleus and cytoplasm and when overexpressed induces apoptosis that is inhibited by CrmA but not Bcl-2 expression. Mutational analysis revealed that the intracellular activity was independent of receptor interaction and activation and reliant on a conserved leucine-rich motif that was not required for activation of cell surface receptors by extracellular protein. This provides the first report of alternate intracellular and extracellular cytokine activities that result from differential cellular localization of the protein and are mediated by spatially distinct motifs.en
dc.language.isoenen
dc.publisherAmerican Society for Cell Biologyen
dc.rightsCopyright © 2000 by The American Society for Cell Biologyen
dc.source.urihttp://www.molbiolcell.org/cgi/content/abstract/11/4/1369en
dc.titleIntracellular and extracellular leukemia inhibitory factor proteins have different cellular activities that are mediated by distinct protein motifsen
dc.typeJournal articleen
dc.contributor.schoolSchool of Molecular and Biomedical Scienceen
dc.contributor.organisationCentre for the Molecular Genetics of Developmenten
Appears in Collections:Centre for the Molecular Genetics of Development publications
Molecular and Biomedical Science publications

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