title: RSK phosphorylates SOS1 creating 14-3-3-docking sites and negatively regulating MAPK activation.
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.
authors: Department of Biology, University of Vermont, Burlington, VT 05405, USA.
authors: Madhurima
authors: M
authors: Saha
authors: Audrey
authors: A
authors: Carriere
authors: Mujeeburahiman
authors: M
authors: Cheerathodi
authors: Xiaocui
authors: X
authors: Zhang
authors: Geneviève
authors: G
authors: Lavoie
authors: John
authors: J
authors: Rush
authors: Philippe P
authors: PP
authors: Roux
authors: Bryan A
authors: BA
authors: Ballif
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D057809:HEK293 Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism*; D020837:SOS1 Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000737:chemistry
chemical_list: D048948:14-3-3 Proteins; D011994:Recombinant Proteins; D020837:SOS1 Protein; D012694:Serine; D019893:Ribosomal Protein S6 Kinases