p90 ribosomal S6 kinase 2 is associated with and dephosphorylated by protein phosphatase 2Cs

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DOIResolve DOI: http://doi.org/10.1042/BJ20040948
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TypeArticle
Journal titleBiochemical Journal
Volume382
IssuePt2
Pages425431; # of pages: 7
Subjectpha; phosphatase; ribosomal; AGC kinase; extracellular-signal-regulated kinase (ERK); mitogen- and stress-activated kinase (MSK); protein phosphatase 2C (PP2C); p90 ribosomal S6 kinase (RSK)
AbstractRSK2 (p90 ribosomal S6 kinase 2) is activated via the ERK (extracellular-signal-regulated kinase) pathway by phosphorylation on four sites: Ser²²⁷ in the activation loop of the N-terminal kinase domain, Ser³⁶⁹ in the linker, Ser³⁸⁶ in the hydrophobic motif and Thr⁵⁷⁷ in the C-terminal kinase domain of RSK2. In the present study, we demonstrate that RSK2 is associated in vivo with PP2Cδ (protein phosphatase 2Cδ). In epidermal growth factorstimulated cells, RSK2 is partially dephosphorylated on all four sites in an Mn²⁺-dependent manner, leading to reduced protein kinase activity. Furthermore, PP2Cδ is phosphorylated by ERK on Thr³¹⁵ and Thr³³³ in the catalytic domain. Mutation of Thr³¹⁵ and Thr³³³ to alanine in a catalytically inactive mutant PP2Cδ(H154D) (His¹⁵⁴→Asp) increases the association with RSK2 significantly, whereas mutation to glutamate, mimicking phosphorylation, reduces the binding of RSK2. The domains of interaction are mapped to the N-terminal extension comprising residues 1–71 of PP2Cδ and the N-terminal kinase domain of RSK2. The interaction is specific, since PP2Cd associates with RSK1–RSK4, MSK1 (mitogen- and stress-activated kinase 1) and MSK2, but not with p70 S6 kinase or phosphoinositide-dependent kinase 1. We conclude that RSK2 is associated with PP2Cδ in vivo and is partially dephosphorylated by it, leading to reduced kinase activity.
Publication date
AffiliationNRC Biotechnology Research Institute; National Research Council Canada
Peer reviewedNo
NRC number46228
NPARC number3539969
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Record identifierc74d7f0d-a932-41ac-83e4-03e84b740b20
Record created2009-03-01
Record modified2016-05-09
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