| First Author | Saha M | Year | 2012 |
| Journal | Biochem J | Volume | 447 |
| Issue | 1 | Pages | 159-66 |
| PubMed ID | 22827337 | Mgi Jnum | J:192971 |
| Mgi Id | MGI:5467173 | Doi | 10.1042/BJ20120938 |
| Citation | Saha M, et al. (2012) RSK phosphorylates SOS1 creating 14-3-3-docking sites and negatively regulating MAPK activation. Biochem J 447(1):159-66 |
| abstractText | 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. |
