Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/23342
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Type: Journal article
Title: Growth factor pleiotropy is controlled by a receptor Tyr/Ser motif that acts as a binary switch
Author: Guthridge, M.
Powell, J.
Barry, E.
Stomski, F.
Mc Clure, B.
Ramshaw, H.
Felquer, F.
Dottore, M.
Thomas, D.
To, L.
Begley, C.
Lopez, A.
Citation: EMBO Journal, 2006; 25(3):479-489
Publisher: Nature Publishing Group
Issue Date: 2006
ISSN: 0261-4189
1460-2075
Statement of
Responsibility: 
Mark 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 Lopez
Abstract: Pleiotropism 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.
Keywords: cell proliferation; cell survival; cytokine; receptors; 14-3-3
Description: Copyright © 2006 by the European Molecular Biology Organization
RMID: 0020060148
DOI: 10.1038/sj.emboj.7600948
Appears in Collections:Medicine publications

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