RSK phosphorylates SOS1 creating 14-3-3-docking sites and negatively regulating MAPK activation.
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Saha M, Carriere A, Cheerathodi M, Zhang X, Lavoie G, Rush J, Roux PP, Ballif BA
RSK phosphorylates SOS1 creating 14-3-3-docking sites and negatively regulating MAPK activation.
Biochem J. 2012 Oct 1;447(1):159-66. doi: 10.1042/BJ20120938.
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- 22827337 [ View in PubMed]
- 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.