Activation of extracellular signal-regulated kinases Erk-1 and Erk-2 by cell swelling in H4IIE hepatoma cells.


Hepatic metabolism and gene expression are among the factors controlled by the cellular hydration state, which changes within minutes in response to aniso-osmotic environments, cumulative substrate uptake, oxidative stress and under the influence of hormones such as insulin. The signalling events coupling cell-volume changes to altered cell function were studied in H4IIE rat hepatoma cells. Hypo-osmotic cell swelling resulted within 1 min in a tyrosine kinase-mediated activation of the extracellular signal-regulated protein kinases Erk-1 and Erk-2, which was independent of protein kinase C and cytosolic calcium. Activation of mitogen-activated protein kinases was followed by an increased phosphorylation of c-Jun, which may explain our recently reported finding of an about 5-fold increase in c-jun mRNA level in response to cell swelling. Pretreatment of cells with pertussis or cholera toxin abolished the swelling-induced activation of Erk-1 and Erk-2, suggesting the involvement of G-proteins. Thus, a signal-transduction pathway resembling growth factor signalling is activated already by osmotic water shifts across the plasma membrane, thereby providing a new perspective for adaption of cell function to alterations of the environment.


Citations per Year

527 Citations

Semantic Scholar estimates that this publication has 527 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Schliess1995ActivationOE, title={Activation of extracellular signal-regulated kinases Erk-1 and Erk-2 by cell swelling in H4IIE hepatoma cells.}, author={Freimut Schliess and Rainer Schreiber and Dieter H{\"a}ussinger}, journal={The Biochemical journal}, year={1995}, volume={309 ( Pt 1)}, pages={13-7} }