Human Intestine 407 cells respond to hypo-osmotic stress with a rapid stimulation of compensatory ionic conductances accompanied by a transient increase in the activity of the extracellular-signal-regulated protein kinases Erk-1 and Erk-2. In this study, we examined the upstream regulators of hypotonicity-induced Erk-1/Erk-2 activation and their possible role in cell-volume regulation. The hypotonicity-provoked Erk-1/Erk-2 activation was greatly reduced in cells pretreated with the specific mitogen-activated/Erk-activating kinase inhibitor PD098059 and was preceded by a transient stimulation of Raf-1. Pretreatment of the cells with PMA, GF 109203X, wortmannin or Clostridium botulinum C3 exoenzyme did not appreciably affect the hypotonicity-provoked Erk-1/Erk-2 stimulation, suggesting the osmosensitive signalling pathway to be largely independent of protein kinase C and p21rho. In contrast, expression of dominant negative RasN17 completely abolished the hypotonicity-induced Erk-1/Erk-2 activation. Stimulation of the swelling-induced ion efflux was independent of activation of these mitogen-activated protein kinases, as revealed by hypotonicity-provoked isotope efflux from 125I-- and 86Rb+-loaded cells after pretreatment with PD098059 and after expression of RasN17. In addition, the epidermal-growth-factor-induced potentiation of the hypotonicity-provoked anionic response did not depend on the increase in Erk-1/Erk-2 activity but, instead, was found to depend on Ca2+ influx. Taken together, these results indicate that hypotonic stress induces Erk-1/Erk-2 activation through the Ras/Raf-signalling pathway, and argue against a direct role for this pathway in cell-volume control.
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Research Article|
May 01 1998
Osmotic swelling-induced activation of the extracellular-signal-regulated protein kinases Erk-1 and Erk-2 in Intestine 407 cells involves the Ras/Raf-signalling pathway
Thea van Der WIJK;
Thea van Der WIJK
1
*Department of Biochemistry, Cardiovascular Research Institute COEUR, Faculty of Medicine and Health Sciences, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands
1To whom correspondence should be addressed (e-mail vanderwijk@bc1.fgg.eur.nl).
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Jannette DORRESTIJN;
Jannette DORRESTIJN
†Department of Molecular Cell Biology, Section Signal Transduction, Leiden University, Leiden, The Netherlands
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Shuh NARUMIYA;
Shuh NARUMIYA
‡Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto, Japan
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J. Antonie MAASSEN;
J. Antonie MAASSEN
†Department of Molecular Cell Biology, Section Signal Transduction, Leiden University, Leiden, The Netherlands
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Hugo R. De JONGE;
Hugo R. De JONGE
*Department of Biochemistry, Cardiovascular Research Institute COEUR, Faculty of Medicine and Health Sciences, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands
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Ben C. TILLY
Ben C. TILLY
*Department of Biochemistry, Cardiovascular Research Institute COEUR, Faculty of Medicine and Health Sciences, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands
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Publisher: Portland Press Ltd
Received:
September 26 1997
Revision Received:
January 14 1998
Accepted:
February 06 1998
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1998
1998
Biochem J (1998) 331 (3): 863–869.
Article history
Received:
September 26 1997
Revision Received:
January 14 1998
Accepted:
February 06 1998
Citation
Thea van Der WIJK, Jannette DORRESTIJN, Shuh NARUMIYA, J. Antonie MAASSEN, Hugo R. De JONGE, Ben C. TILLY; Osmotic swelling-induced activation of the extracellular-signal-regulated protein kinases Erk-1 and Erk-2 in Intestine 407 cells involves the Ras/Raf-signalling pathway. Biochem J 1 May 1998; 331 (3): 863–869. doi: https://doi.org/10.1042/bj3310863
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