Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/23342
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dc.contributor.authorGuthridge, M.en
dc.contributor.authorPowell, J.en
dc.contributor.authorBarry, E.en
dc.contributor.authorStomski, F.en
dc.contributor.authorMc Clure, B.en
dc.contributor.authorRamshaw, H.en
dc.contributor.authorFelquer, F.en
dc.contributor.authorDottore, M.en
dc.contributor.authorThomas, D.en
dc.contributor.authorTo, L.en
dc.contributor.authorBegley, C.en
dc.contributor.authorLopez, A.en
dc.date.issued2006en
dc.identifier.citationEMBO Journal, 2006; 25(3):479-489en
dc.identifier.issn0261-4189en
dc.identifier.issn1460-2075en
dc.identifier.urihttp://hdl.handle.net/2440/23342-
dc.descriptionCopyright © 2006 by the European Molecular Biology Organizationen
dc.description.abstractPleiotropism is a hallmark of cytokines and growth factors; yet, the underlying mechanisms are not clearly understood. We have identified a motif in the granulocyte macrophage-colony-stimulating factor receptor composed of a tyrosine and a serine residue that functions as a binary switch for the independent regulation of multiple biological activities. Signalling occurs either through Ser585 at lower cytokine concentrations, leading to cell survival only, or through Tyr577 at higher cytokine concentrations, leading to cell survival as well as proliferation, differentiation or functional activation. The phosphorylation of Ser585 and Tyr577 is mutually exclusive and occurs via a unidirectional mechanism that involves protein kinase A and tyrosine kinases, respectively, and is deregulated in at least some leukemias. We have identified similar Tyr/Ser motifs in other cell surface receptors, suggesting that such signalling switches may play important roles in generating specificity and pleiotropy in other biological systems.en
dc.description.statementofresponsibilityMark A Guthridge, Jason A Powell, Emma F Barry, Frank C Stomski, Barbara J McClure, Hayley Ramshaw, Fernando A Felquer, Mara Dottore, Daniel T Thomas, Bik To, C Glenn Begley and Angel F Lopezen
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.subjectcell proliferation; cell survival; cytokine; receptors; 14-3-3en
dc.titleGrowth factor pleiotropy is controlled by a receptor Tyr/Ser motif that acts as a binary switchen
dc.typeJournal articleen
dc.identifier.rmid0020060148en
dc.identifier.doi10.1038/sj.emboj.7600948en
dc.identifier.pubid53202-
pubs.library.collectionMedicine publicationsen
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
dc.identifier.orcidRamshaw, H. [0000-0001-9909-282X]en
dc.identifier.orcidLopez, A. [0000-0001-7430-0135]en
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