PMID- 10480933
OWN - NLM
STAT- MEDLINE
DCOM- 19991013
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 38
DP  - 1999 Sep 17
TI  - 90-kDa ribosomal S6 kinase is phosphorylated and activated by
      3-phosphoinositide-dependent protein kinase-1.
PG  - 27168-76
AB  - 90-kDa ribosomal S6 kinase-2 (RSK2) belongs to a family of growth
      factor-activated serine/threonine kinases composed of two kinase domains
      connected by a regulatory linker region. The N-terminal kinase of RSK2 is
      involved in substrate phosphorylation. Its activation requires phosphorylation of
      the linker region at Ser(369), catalyzed by extracellular signal-regulated kinase
      (ERK), and at Ser(386), catalyzed by the C-terminal kinase, after its activation 
      by ERK. In addition, the N-terminal kinase must be phosphorylated at Ser(227) in 
      the activation loop by an as yet unidentified kinase. Here, we show that the
      isolated N-terminal kinase of RSK2 (amino acids 1-360) is phosphorylated at
      Ser(227) by PDK1, a constitutively active kinase, leading to 100-fold stimulation
      of kinase activity. In COS7 cells, ectopic PDK1 induced the phosphorylation of
      full-length RSK2 at Ser(227) and Ser(386), without involvement of ERK, leading to
      partial activation of RSK2. Similarly, two other members of the RSK family, RSK1 
      and RSK3, were partially activated by PDK1 in COS7 cells. Finally, our data
      indicate that full activation of RSK2 by growth factor requires the cooperation
      of ERK and PDK1 through phosphorylation of Ser(227), Ser(369), and Ser(386). Our 
      study extend recent findings which implicate PDK1 in the activation of protein
      kinases B and C and p70(S6K), suggesting that PDK1 controls several major growth 
      factor-activated signal transduction pathways.
FAU - Jensen, C J
AU  - Jensen CJ
AD  - Department of Clinical Biochemistry, Glostrup Hospital, DK-2600 Glostrup,
      Denmark.
FAU - Buch, M B
AU  - Buch MB
FAU - Krag, T O
AU  - Krag TO
FAU - Hemmings, B A
AU  - Hemmings BA
FAU - Gammeltoft, S
AU  - Gammeltoft S
FAU - Frodin, M
AU  - Frodin M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.1 (3-Phosphoinositide-Dependent Protein Kinases)
RN  - EC 2.7.11.1 (PDPK1 protein, human)
RN  - EC 2.7.11.1 (Pdpk1 protein, mouse)
RN  - EC 2.7.11.1 (Pdpk1 protein, rat)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
SB  - IM
MH  - 3-Phosphoinositide-Dependent Protein Kinases
MH  - Amino Acid Sequence
MH  - Animals
MH  - COS Cells
MH  - Enzyme Activation
MH  - Humans
MH  - Mice
MH  - Molecular Sequence Data
MH  - Phosphorylation
MH  - Protein-Serine-Threonine Kinases/*metabolism
MH  - Rats
MH  - Ribosomal Protein S6 Kinases/*metabolism
MH  - Serine/metabolism
EDAT- 1999/09/10 00:00
MHDA- 1999/09/10 00:01
CRDT- 1999/09/10 00:00
PHST- 1999/09/10 00:00 [pubmed]
PHST- 1999/09/10 00:01 [medline]
PHST- 1999/09/10 00:00 [entrez]
AID - 10.1074/jbc.274.38.27168 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Sep 17;274(38):27168-76. doi: 10.1074/jbc.274.38.27168.