We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
RSK phosphorylates SOS1 creating 14-3-3-docking sites and negatively regulating MAPK activation.
- Authors
Saha, Madhurima; Carriere, Audrey; Cheerathodi, Mujeeburahiman; Zhang, Xiaocui; Lavoie, Geneviève; Rush, John; Roux, Philippe P; Ballif, Bryan A
- Abstract
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, Ser(1134) and Ser(1161). Furthermore, we find that RSK-dependent SOS1 phosphorylation creates 14-3-3-binding sites. We show that mutating Ser(1134) and Ser(1161) 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.
- Publication
The Biochemical journal, 2012, Vol 447, Issue 1, p159
- ISSN
1470-8728
- Publication type
Journal Article
- DOI
10.1042/BJ20120938