Regulation of Na+ reabsorption by the aldosterone-induced small G protein K-Ras2A

James D. Stockand, Bret J. Spier, Roger T. Worrell, Gang Yue, Nabil Al-Baldawi, Douglas C. Eaton

Research output: Contribution to journalArticlepeer-review

80 Scopus citations


Xenopus laevis A6 cells were used as model epithelia to test the hypothesis that K-Ras2A is an aldosterone-induced protein necessary for steroid-regulated Na+ transport. The possibility that increased K-Ras2A alone is sufficient to mimic aldosterone action on Na+ transport also was tested. Aldosterone treatment increased K-Ras2A protein expression 2.8-fold within 4 h. Active Ras is membrane associated. After aldosterone treatment, 75% of K-Ras was localized to the plasma membrane compared with 25% in the absence of steroid. Aldosterone also increased the amount of active (phosphorylated) mitogen-activated protein kinase kinase likely through K- Ras2A signaling. Steroid-induced K-Ras2A protein levels and Na+ transport were decreased with antisense K-ras2A oligonucleotides, showing that K-Ras2A is necessary for the natriferic actions of aldosterone. Aldosterone-induced Na+ channel activity, was decreased from 0.40 to 0.09 by pretreatment with antisense ras oligonucleotide, implicating the luminal Na+ channel as one final effector of Ras signaling. Overexpression of K-Ras2A increased Na+ transport approximately 2.2-fold in the absence of aldosterone. These results suggest that aldosterone signals to the luminal Na+ channel via multiple pathways and that K-Ras2A levels are limiting for a portion of the aldosterone-sensitive Na+ transport.

Original languageEnglish (US)
Pages (from-to)35449-35454
Number of pages6
JournalJournal of Biological Chemistry
Issue number50
StatePublished - Dec 10 1999
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry
  • Cell Biology


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