PMID- 15206906
OWN - NLM
STAT- MEDLINE
DCOM- 20050222
LR  - 20220311
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Print)
IS  - 0264-6021 (Linking)
VI  - 382
IP  - Pt 2
DP  - 2004 Sep 1
TI  - p90 ribosomal S6 kinase 2 is associated with and dephosphorylated by protein 
      phosphatase 2Cdelta.
PG  - 425-31
AB  - 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 PP2Cdelta (protein phosphatase 2Cdelta). 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, PP2Cd is phosphorylated by ERK on Thr315 and Thr333 in the catalytic 
      domain. Mutation of Thr315 and Thr333 to alanine in a catalytically inactive 
      mutant PP2Cdelta (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 PP2Cd 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 
      PP2Cd in vivo and is partially dephosphorylated by it, leading to reduced kinase 
      activity.
FAU - Doehn, Ulrik
AU  - Doehn U
AD  - Department of Clinical Biochemistry, Glostrup Hospital, DK 2600 Glostrup, 
      Denmark. ud@dcb-glostrup.dk
FAU - Gammeltoft, Steen
AU  - Gammeltoft S
FAU - Shen, Shi-Hsiang
AU  - Shen SH
FAU - Jensen, Claus J
AU  - Jensen CJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Peptides)
RN  - EC 2.7.- (Phosphotransferases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 90-kDa)
RN  - EC 2.7.11.1 (ribosomal protein S6 kinase, 90kDa, polypeptide 3)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
SB  - IM
MH  - Animals
MH  - COS Cells/chemistry/enzymology/metabolism
MH  - Catalytic Domain/physiology
MH  - Cell Line
MH  - Chlorocebus aethiops
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Humans
MH  - Kidney/cytology/embryology/enzymology
MH  - Mutation/genetics/physiology
MH  - Peptides/metabolism/physiology
MH  - Phosphoprotein Phosphatases/genetics/*metabolism
MH  - Phosphorylation
MH  - Phosphotransferases/metabolism
MH  - Protein Interaction Mapping/methods
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Protein Structure, Tertiary/physiology
MH  - Ribosomal Protein S6 Kinases, 90-kDa/*metabolism
PMC - PMC1133798
EDAT- 2004/06/23 05:00
MHDA- 2005/02/23 09:00
PMCR- 2005/03/01
CRDT- 2004/06/23 05:00
PHST- 2004/06/18 00:00 [accepted]
PHST- 2004/06/07 00:00 [received]
PHST- 2004/06/23 05:00 [pubmed]
PHST- 2005/02/23 09:00 [medline]
PHST- 2004/06/23 05:00 [entrez]
PHST- 2005/03/01 00:00 [pmc-release]
AID - BJ20040948 [pii]
AID - bj3820425 [pii]
AID - 10.1042/BJ20040948 [doi]
PST - ppublish
SO  - Biochem J. 2004 Sep 1;382(Pt 2):425-31. doi: 10.1042/BJ20040948.