The extent and duration of MAPK (mitogen-activated protein kinase) signalling govern a diversity of normal and aberrant cellular outcomes. Genetic and pharmacological disruption of the MAPK-activated kinase RSK (ribosomal S6 kinase) leads to elevated MAPK activity indicative of a RSK-dependent negative feedback loop. Using biochemical, pharmacological and quantitative MS approaches we show that RSK phosphorylates the Ras activator SOS1 (Son of Sevenless homologue 1) in cultured cells on two C-terminal residues, Ser1134 and Ser1161. Furthermore, we find that RSK-dependent SOS1 phosphorylation creates 14-3-3-binding sites. We show that mutating Ser1134 and Ser1161 disrupts 14-3-3 binding and modestly increases and extends MAPK activation. Together these data suggest that one mechanism whereby RSK negatively regulates MAPK activation is via site-specific SOS1 phosphorylation.
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October 2012
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Research Article|
September 12 2012
RSK phosphorylates SOS1 creating 14-3-3-docking sites and negatively regulating MAPK activation
Madhurima Saha;
Madhurima Saha
*Department of Biology, University of Vermont, Burlington, VT 05405, U.S.A.
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Audrey Carriere;
Audrey Carriere
1
†Institute for Research in Immunology and Cancer (IRIC), Montréal, Québec, Canada, H3C 3J7
‡Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada, H3C 3J7
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Mujeeburahiman Cheerathodi;
Mujeeburahiman Cheerathodi
*Department of Biology, University of Vermont, Burlington, VT 05405, U.S.A.
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Xiaocui Zhang;
Xiaocui Zhang
†Institute for Research in Immunology and Cancer (IRIC), Montréal, Québec, Canada, H3C 3J7
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Geneviève Lavoie;
Geneviève Lavoie
†Institute for Research in Immunology and Cancer (IRIC), Montréal, Québec, Canada, H3C 3J7
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John Rush;
John Rush
§Cell Signaling Technology, Inc., 3 Trask Lane, Danvers, MA 01923, U.S.A.
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Philippe P. Roux;
Philippe P. Roux
2
†Institute for Research in Immunology and Cancer (IRIC), Montréal, Québec, Canada, H3C 3J7
‡Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada, H3C 3J7
2Correspondence may be addressed to either of these authors (email [email protected] or [email protected]).
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Bryan A. Ballif
Bryan A. Ballif
2
*Department of Biology, University of Vermont, Burlington, VT 05405, U.S.A.
2Correspondence may be addressed to either of these authors (email [email protected] or [email protected]).
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Publisher: Portland Press Ltd
Received:
June 07 2012
Revision Received:
July 24 2012
Accepted:
July 25 2012
Accepted Manuscript online:
July 25 2012
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biochem J (2012) 447 (1): 159–166.
Article history
Received:
June 07 2012
Revision Received:
July 24 2012
Accepted:
July 25 2012
Accepted Manuscript online:
July 25 2012
Connected Content
A correction has been published:
Correction: RSK phosphorylates SOS1 creating 14-3-3-docking sites and negatively regulating MAPK activation
Citation
Madhurima Saha, Audrey Carriere, Mujeeburahiman Cheerathodi, Xiaocui Zhang, Geneviève Lavoie, John Rush, Philippe P. Roux, Bryan A. Ballif; RSK phosphorylates SOS1 creating 14-3-3-docking sites and negatively regulating MAPK activation. Biochem J 1 October 2012; 447 (1): 159–166. doi: https://doi.org/10.1042/BJ20120938
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