RSK2 (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 PP2Cδ 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.
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September 2004
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Research Article|
August 24 2004
p90 ribosomal S6 kinase 2 is associated with and dephosphorylated by protein phosphatase 2Cδ
Ulrik DOEHN;
Ulrik DOEHN
1
*Department of Clinical Biochemistry, Glostrup Hospital, DK 2600 Glostrup, Denmark
1To whom correspondence should be addressed (email [email protected]).
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Steen GAMMELTOFT;
Steen GAMMELTOFT
*Department of Clinical Biochemistry, Glostrup Hospital, DK 2600 Glostrup, Denmark
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Shi-Hsiang SHEN;
Shi-Hsiang SHEN
†Biotechnology Research Institute, National Research Council of Canada, Montreal, Quebec, Canada H4P 2R2
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Claus J. JENSEN
Claus J. JENSEN
*Department of Clinical Biochemistry, Glostrup Hospital, DK 2600 Glostrup, Denmark
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Publisher: Portland Press Ltd
Received:
June 07 2004
Accepted:
June 18 2004
Accepted Manuscript online:
June 18 2004
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2004
Biochem J (2004) 382 (2): 425–431.
Article history
Received:
June 07 2004
Accepted:
June 18 2004
Accepted Manuscript online:
June 18 2004
Citation
Ulrik DOEHN, Steen GAMMELTOFT, Shi-Hsiang SHEN, Claus J. JENSEN; p90 ribosomal S6 kinase 2 is associated with and dephosphorylated by protein phosphatase 2Cδ. Biochem J 1 September 2004; 382 (2): 425–431. doi: https://doi.org/10.1042/BJ20040948
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