Hypotonicity activates transcription through ERK-dependent and - independent pathways in renal cells

Zheng Zhang, Xiao Yan Yang, David M. Cohen

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Acute hypotonic shock (50% dilution of medium with sterile water, but not with isotonic NaCl) activated the extracellular signal response kinase (ERK) mitogen-activated protein (MAP) kinases in renal medullary cells, as measured by Western analysis with a phospho-ERK-specific antibody and by in vitro kinase assay of epitope-tagged ERKs immunoprecipitated from stable HA- ERK transfectants. Hypotonicity also activated the transcription factor and ERK substrate Elk-1 in a partially PD-98059-sensitive fashion, as assessed by chimetic reporter gene assay. Consistent with these data, hypotonic stress activated transcription of the immediate-early gene transcription factor Egr- 1 in a partially PD-98059-sensitive fashion. Hypotonicity-inducible Egr-1 transcription was mediated in part through 5'-flanking regions containing serum response elements and in part through the minimal Egr-1 promoter. Elimination of the Ets motifs adjacent to key regulatory serum response elements in the Egr-1 promoter diminished the effect of hypotonicity but failed to abolish it. Interestingly, hypotonicity also transiently activated p38 and c-Jun NH2-terminal kinase 1, as determined by immunoblotting with anti-phospho-MAP kinase antibodies. Taken together, these data strongly suggest that hypotonicity activates immediate-early gene transcription in renal medullary cells via MAP kinase kinase-dependent and -independent mechanisms.

Original languageEnglish (US)
Pages (from-to)C1104-C1112
JournalAmerican Journal of Physiology - Cell Physiology
Issue number4 44-4
StatePublished - Oct 1998


  • C- Jun amino-terminal kinase
  • Kidney
  • P38
  • Signal transduction
  • Stress-activated protein kinase
  • Urea

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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