HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stockand, J. D. Articles by Eaton, D. C. Search for Related Content PubMed PubMed Citation Articles by Stockand, J. D. Articles by Eaton, D. C.

J Biol Chem, Vol. 274, Issue 50, 35449-35454, December 10, 1999

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, and Douglas C. Eaton

From the Center for Cell and Molecular Signaling, Department of Physiology, Emory University School of Medicine, Atlanta, Georgia 30322

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.

---

^* This work was supported by National Institutes of Health Grants DK09729 (to J. D. S.) and DK37963 (to D. C. E.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Center for Cell and Molecular Signaling, Dept. of Physiology, Emory University School of Medicine, 1648 Pierce Dr., Atlanta, GA 30322. Tel.: 404-727-7427; Fax: 404-727-0329; E-mail: jstocka@emory.edu.

---

Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

This article has been cited by other articles:

				O. Pochynyuk, J. D. Stockand, and A. Staruschenko Ion Channel Regulation by Ras, Rho, and Rab Small GTPases Experimental Biology and Medicine, November 1, 2007; 232(10): 1258 - 1265. [Abstract] [Full Text] [PDF]

				A. Staruschenko, O. Pochynyuk, A. Vandewalle, V. Bugaj, and J. D. Stockand Acute Regulation of the Epithelial Na+ Channel by Phosphatidylinositide 3-OH Kinase Signaling in Native Collecting Duct Principal Cells J. Am. Soc. Nephrol., June 1, 2007; 18(6): 1652 - 1661. [Abstract] [Full Text] [PDF]

				J. L. Holzman, L. Liu, B. J. Duke, A. E. Kemendy, and D. C. Eaton Transactivation of the IGF-1R by aldosterone Am J Physiol Renal Physiol, April 1, 2007; 292(4): F1219 - F1228. [Abstract] [Full Text] [PDF]

				F. E. Brennan and P. J. Fuller Mammalian K-ras2 Is a Corticosteroid-Induced Gene in Vivo Endocrinology, June 1, 2006; 147(6): 2809 - 2816. [Abstract] [Full Text] [PDF]

				O. Pochynyuk, Q. Tong, A. Staruschenko, H.-P. Ma, and J. D. Stockand Regulation of the epithelial Na+ channel (ENaC) by phosphatidylinositides Am J Physiol Renal Physiol, May 1, 2006; 290(5): F949 - F957. [Abstract] [Full Text] [PDF]

				R. S. Edinger, J. Yospin, C. Perry, T. R. Kleyman, and J. P. Johnson Regulation of Epithelial Na+ Channels (ENaC) by Methylation: A NOVEL METHYLTRANSFERASE STIMULATES ENaC ACTIVITY J. Biol. Chem., April 7, 2006; 281(14): 9110 - 9117. [Abstract] [Full Text] [PDF]

				M. N. Helms, X.-J. Chen, S. Ramosevac, D. C. Eaton, and L. Jain Dopamine regulation of amiloride-sensitive sodium channels in lung cells Am J Physiol Lung Cell Mol Physiol, April 1, 2006; 290(4): L710 - L722. [Abstract] [Full Text] [PDF]

				O. Pochynyuk, A. Staruschenko, Q. Tong, J. Medina, and J. D. Stockand Identification of a Functional Phosphatidylinositol 3,4,5-Trisphosphate Binding Site in the Epithelial Na+ Channel J. Biol. Chem., November 11, 2005; 280(45): 37565 - 37571. [Abstract] [Full Text] [PDF]

				H.-P. Ma and D. C. Eaton Acute Regulation of Epithelial Sodium Channel by Anionic Phospholipids J. Am. Soc. Nephrol., November 1, 2005; 16(11): 3182 - 3187. [Abstract] [Full Text] [PDF]

				L.-J. Min, M. Mogi, J.-M. Li, J. Iwanami, M. Iwai, and M. Horiuchi Aldosterone and Angiotensin II Synergistically Induce Mitogenic Response in Vascular Smooth Muscle Cells Circ. Res., September 2, 2005; 97(5): 434 - 442. [Abstract] [Full Text] [PDF]

				Y. Terada, T. Kobayashi, H. Kuwana, H. Tanaka, S. Inoshita, M. Kuwahara, and S. Sasaki Aldosterone Stimulates Proliferation of Mesangial Cells by Activating Mitogen-Activated Protein Kinase 1/2, Cyclin D1, and Cyclin A J. Am. Soc. Nephrol., August 1, 2005; 16(8): 2296 - 2305. [Abstract] [Full Text] [PDF]

				C. Grossmann, A. Benesic, A. W. Krug, R. Freudinger, S. Mildenberger, B. Gassner, and M. Gekle Human Mineralocorticoid Receptor Expression Renders Cells Responsive for Nongenotropic Aldosterone Actions Mol. Endocrinol., July 1, 2005; 19(7): 1697 - 1710. [Abstract] [Full Text] [PDF]

				Q. Tong and J. D. Stockand Receptor tyrosine kinases mediate epithelial Na+ channel inhibition by epidermal growth factor Am J Physiol Renal Physiol, January 1, 2005; 288(1): F150 - F161. [Abstract] [Full Text] [PDF]

				F. Mies, V. Shlyonsky, A. Goolaerts, and S. Sariban-Sohraby Modulation of epithelial Na+ channel activity by long-chain n-3 fatty acids Am J Physiol Renal Physiol, October 1, 2004; 287(4): F850 - F855. [Abstract] [Full Text] [PDF]

				A. Staruschenko, P. Patel, Q. Tong, J. L. Medina, and J. D. Stockand Ras Activates the Epithelial Na+ Channel through Phosphoinositide 3-OH Kinase Signaling J. Biol. Chem., September 3, 2004; 279(36): 37771 - 37778. [Abstract] [Full Text] [PDF]

				Q. Tong, R. E. Booth, R. T. Worrell, and J. D. Stockand Regulation of Na+ transport by aldosterone: signaling convergence and cross talk between the PI3-K and MAPK1/2 cascades Am J Physiol Renal Physiol, June 1, 2004; 286(6): F1232 - F1238. [Abstract] [Full Text] [PDF]

				Q. Tong, N. Gamper, J. L. Medina, M. S. Shapiro, and J. D. Stockand Direct Activation of the Epithelial Na+ Channel by Phosphatidylinositol 3,4,5-Trisphosphate and Phosphatidylinositol 3,4-Bisphosphate Produced by Phosphoinositide 3-OH Kinase J. Biol. Chem., May 21, 2004; 279(21): 22654 - 22663. [Abstract] [Full Text] [PDF]

				P. M. Snyder, J. C. Steines, and D. R. Olson Relative Contribution of Nedd4 and Nedd4-2 to ENaC Regulation in Epithelia Determined by RNA Interference J. Biol. Chem., February 6, 2004; 279(6): 5042 - 5046. [Abstract] [Full Text] [PDF]

				R. E. Booth, Q. Tong, J. Medina, P. M. Snyder, P. Patel, and J. D. Stockand A Region Directly Following the Second Transmembrane Domain in {gamma}ENaC Is Required for Normal Channel Gating J. Biol. Chem., October 17, 2003; 278(42): 41367 - 41379. [Abstract] [Full Text] [PDF]

				R. E. Booth and J. D. Stockand Targeted degradation of ENaC in response to PKC activation of the ERK1/2 cascade Am J Physiol Renal Physiol, May 1, 2003; 284(5): F938 - F947. [Abstract] [Full Text] [PDF]

				J. D. Stockand and J. G. Meszaros Aldosterone stimulates proliferation of cardiac fibroblasts by activating Ki-RasA and MAPK1/2 signaling Am J Physiol Heart Circ Physiol, January 1, 2003; 284(1): H176 - H184. [Abstract] [Full Text] [PDF]

				A. W. Krug, C. Schuster, B. Gassner, R. Freudinger, S. Mildenberger, J. Troppmair, and M. Gekle Human Epidermal Growth Factor Receptor-1 Expression Renders Chinese Hamster Ovary Cells Sensitive to Alternative Aldosterone Signaling J. Biol. Chem., November 22, 2002; 277(48): 45892 - 45897. [Abstract] [Full Text] [PDF]

				A. Becchetti, B. Malik, G. Yue, P. Duchatelle, O. Al-Khalili, T. R. Kleyman, and D. C. Eaton Phosphatase inhibitors increase the open probability of ENaC in A6 cells Am J Physiol Renal Physiol, November 1, 2002; 283(5): F1030 - F1045. [Abstract] [Full Text] [PDF]

				E. Hendron, P. Patel, M. Hausenfluke, N. Gamper, M. S. Shapiro, R. E. Booth, and J. D. Stockand Identification of Cytoplasmic Domains within the Epithelial Na+ Channel Reactive at the Plasma Membrane J. Biol. Chem., September 6, 2002; 277(37): 34480 - 34488. [Abstract] [Full Text] [PDF]

				E. Hendron and J. D. Stockand Activation of Mitogen-activated Protein Kinase (Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase) Cascade by Aldosterone Mol. Biol. Cell, September 1, 2002; 13(9): 3042 - 3054. [Abstract] [Full Text] [PDF]

				S. Boulkroun, M. Fay, M.-C. Zennaro, B. Escoubet, F. Jaisser, M. Blot-Chabaud, N. Farman, and N. Courtois-Coutry Characterization of Rat NDRG2 (N-Myc Downstream Regulated Gene 2), a Novel Early Mineralocorticoid-specific Induced Gene J. Biol. Chem., August 23, 2002; 277(35): 31506 - 31515. [Abstract] [Full Text] [PDF]

				P. M. Snyder The Epithelial Na+ Channel: Cell Surface Insertion and Retrieval in Na+ Homeostasis and Hypertension Endocr. Rev., April 1, 2002; 23(2): 258 - 275. [Abstract] [Full Text] [PDF]

				J. D. Stockand New ideas about aldosterone signaling in epithelia Am J Physiol Renal Physiol, April 1, 2002; 282(4): F559 - F576. [Abstract] [Full Text] [PDF]

				R. E. Booth, J. P. Johnson, and J. D. Stockand ALDOSTERONE Advan Physiol Educ, March 1, 2002; 26(1): 8 - 20. [Abstract] [Full Text] [PDF]

				J. D. Stockand, S. Zeltwanger, H.-F. Bao, A. Becchetti, R. T. Worrell, and D. C. Eaton S-adenosyl-L-homocysteine hydrolase is necessary for aldosterone-induced activity of epithelial Na+ channels Am J Physiol Cell Physiol, September 1, 2001; 281(3): C773 - C785. [Abstract] [Full Text] [PDF]

				T. R. Kleyman, J. B. Zuckerman, P. Middleton, K. A. McNulty, B. Hu, X. Su, B. An, D. C. Eaton, and P. R. Smith Cell surface expression and turnover of the alpha -subunit of the epithelial sodium channel Am J Physiol Renal Physiol, August 1, 2001; 281(2): F213 - F221. [Abstract] [Full Text] [PDF]

				V. E. Mick, O. A. Itani, R. W. Loftus, R. F. Husted, T. J. Schmidt, and C. P. Thomas The {{alpha}}-Subunit of the Epithelial Sodium Channel Is an Aldosterone-Induced Transcript in Mammalian Collecting Ducts, and This Transcriptional Response Is Mediated via Distinct cis-Elements in the 5'-Flanking Region of the Gene Mol. Endocrinol., April 1, 2001; 15(4): 575 - 588. [Abstract] [Full Text]

				J. Loffing, M. Zecevic, E. Feraille, B. Kaissling, C. Asher, B. C. Rossier, G. L. Firestone, D. Pearce, and F. Verrey Aldosterone induces rapid apical translocation of ENaC in early portion of renal collecting system: possible role of SGK Am J Physiol Renal Physiol, April 1, 2001; 280(4): F675 - F682. [Abstract] [Full Text] [PDF]

				J. D. Stockand, R. S. Edinger, D. C. Eaton, and J. P. Johnson Toward Understanding the Role of Methylation in Aldosterone-Sensitive Na+ Transport Physiology, August 1, 2000; 15(4): 161 - 165. [Abstract] [Full Text] [PDF]

				N. F. Al-Baldawi, J. D. Stockand, O. K. Al-Khalili, G. Yue, and D. C. Eaton Aldosterone induces Ras methylation in A6 epithelia Am J Physiol Cell Physiol, August 1, 2000; 279(2): C429 - C439. [Abstract] [Full Text] [PDF]

				A. Becchetti, A. E. Kemendy, J. D. Stockand, S. Sariban-Sohraby, and D. C. Eaton Methylation Increases the Open Probability of the Epithelial Sodium Channel in A6 Epithelia J. Biol. Chem., May 26, 2000; 275(22): 16550 - 16559. [Abstract] [Full Text] [PDF]

				J. D. Stockand, H.-F. Bao, J. Schenck, B. Malik, P. Middleton, L. E. Schlanger, and D. C. Eaton Differential Effects of Protein Kinase C on the Levels of Epithelial Na+ Channel Subunit Proteins J. Biol. Chem., August 11, 2000; 275(33): 25760 - 25765. [Abstract] [Full Text] [PDF]

				M. Gekle, R. Freudinger, S. Mildenberger, and S. Silbernagl Aldosterone interaction with epidermal growth factor receptor signaling in MDCK cells Am J Physiol Renal Physiol, April 1, 2002; 282(4): F669 - F679. [Abstract] [Full Text] [PDF]