PMID- 10400637
OWN - NLM
STAT- MEDLINE
DCOM- 19990819
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 29
DP  - 1999 Jul 16
TI  - p90(RSK) is a serum-stimulated Na+/H+ exchanger isoform-1 kinase. Regulatory
      phosphorylation of serine 703 of Na+/H+ exchanger isoform-1.
PG  - 20206-14
AB  - The Na+/H+ exchanger isoform-1 (NHE-1) is the key member of a family of
      exchangers that regulates intracellular pH and cell volume. Activation of NHE-1
      by growth factors is rapid, correlates with increased NHE-1 phosphorylation and
      cell alkalinization, and plays a role in cell cycle progression. By
      two-dimensional tryptic peptide mapping of immunoprecipitated NHE-1, we identify 
      serine 703 as the major serum-stimulated amino acid. Mutation of serine 703 to
      alanine had no effect on acid-stimulated Na+/H+ exchange but completely prevented
      the growth factor-mediated increase in NHE-1 affinity for H+. In addition, we
      show that p90 ribosomal S6 kinase (p90(RSK)) is a key NHE-1 kinase since p90(RSK)
      phosphorylates NHE-1 serine 703 stoichiometrically in vitro, and transfection
      with kinase-inactive p90(RSK) inhibits serum-induced phosphorylation of NHE-1
      serine 703 in transfected 293 cells. These findings establish p90(RSK) as a
      serum-stimulated NHE-1 kinase and a mediator of increased Na+/H+ exchange in
      vivo.
FAU - Takahashi, E
AU  - Takahashi E
AD  - Departments of Medicine, University of Washington, Seattle, Washington 98195,
      USA.
FAU - Abe, J
AU  - Abe J
FAU - Gallis, B
AU  - Gallis B
FAU - Aebersold, R
AU  - Aebersold R
FAU - Spring, D J
AU  - Spring DJ
FAU - Krebs, E G
AU  - Krebs EG
FAU - Berk, B C
AU  - Berk BC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA Primers)
RN  - 0 (DNA, Complementary)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Protein Isoforms)
RN  - 0 (Sodium-Hydrogen Exchangers)
RN  - 0 (growth factor-activatable Na-H exchanger NHE-1)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - EC 3.4.21.5 (Thrombin)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Blood
MH  - Cells, Cultured
MH  - DNA Primers
MH  - DNA, Complementary
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/pharmacology
MH  - Flavonoids/pharmacology
MH  - MAP Kinase Kinase 1
MH  - Male
MH  - *Mitogen-Activated Protein Kinase Kinases
MH  - Mutagenesis, Site-Directed
MH  - Peptide Mapping
MH  - Phosphorylation
MH  - Precipitin Tests
MH  - Protein Isoforms/chemistry/genetics/*metabolism
MH  - Protein-Serine-Threonine Kinases/antagonists & inhibitors
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Ribosomal Protein S6 Kinases/genetics/*metabolism
MH  - Serine/*metabolism
MH  - Sodium-Hydrogen Exchangers/chemistry/genetics/*metabolism
MH  - Thrombin/pharmacology
MH  - Transfection
EDAT- 1999/07/10 00:00
MHDA- 1999/07/10 00:01
CRDT- 1999/07/10 00:00
PHST- 1999/07/10 00:00 [pubmed]
PHST- 1999/07/10 00:01 [medline]
PHST- 1999/07/10 00:00 [entrez]
AID - 10.1074/jbc.274.29.20206 [doi]
AID - S0021-9258(19)72638-6 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Jul 16;274(29):20206-14. doi: 10.1074/jbc.274.29.20206.