Urea signaling to ERK phosphorylation in renal medullary cells requires extracellular calcium but not calcium entry

Xiao Yan Yang, Hongyu Zhao, Zheng Zhang, Karin D. Rodland, Jean Baptiste Roullet, David M. Cohen

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The renal cell line mIMCD3 exhibits markedly upregulated phosphorylation of the extracellular signal-regulated kinase (ERK) 1 and 2 in response to urea treatment (200 mM for 5 min). Previous data have suggested the involvement of a classical protein kinase C (cPKC)-dependent pathway in downstream events related to urea signaling. We now show that urea-inducible ERK activation requires extracellular calcium; unexpectedly, it occurs independently of activation of cPKC isoforms. Pharmacological inhibitors of known intracellular calcium release pathways and extracellular calcium entry pathways fail to inhibit ERK activation by urea. Fura 2 ratiometry was used to assess the effect of urea treatment on intracellular calcium mobilization. In single-cell analyses using subconfluent monolayers and in population-wide analyses using both confluent monolayers and cells in suspension, urea failed to increase intracellular calcium concentration. Taken together, these data indicate that urea-inducible ERK activation requires calcium action but not calcium entry. Although direct evidence is lacking, one possible explanation could include involvement of a calcium-dependent extracellular moiety of a cell surface-associated protein.

Original languageEnglish (US)
Pages (from-to)F162-F171
JournalAmerican Journal of Physiology - Renal Physiology
Volume280
Issue number1 49-1
DOIs
StatePublished - Jan 2001

Keywords

  • Fura 2
  • Hypotonicity
  • Inner medullary collecting duct
  • Madin-Darby canine kidney
  • Protein kinase C

ASJC Scopus subject areas

  • Physiology
  • Urology

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