p90(RSK) is a serum-stimulated Na+/H+ exchanger isoform-1 kinase. Regulatory phosphorylation of serine 703 of Na+/H+ exchanger isoform-1
| Autor: | E, Takahashi, J, Abe, B, Gallis, R, Aebersold, D J, Spring, E G, Krebs, B C, Berk |
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| Rok vydání: | 1999 |
| Předmět: |
Male
DNA Complementary Sodium-Hydrogen Exchangers MAP Kinase Kinase 1 Protein Serine-Threonine Kinases Transfection Peptide Mapping Rats Sprague-Dawley Serine Animals Protein Isoforms Amino Acid Sequence Enzyme Inhibitors Phosphorylation Cells Cultured DNA Primers Flavonoids Mitogen-Activated Protein Kinase Kinases Base Sequence Ribosomal Protein S6 Kinases Thrombin Protein-Tyrosine Kinases Precipitin Tests Rats Enzyme Activation Blood Mutagenesis Site-Directed |
| Zdroj: | The Journal of biological chemistry. 274(29) |
| ISSN: | 0021-9258 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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