Hyperosmotic stress strongly potentiates serum response factor (SRF)-dependent transcriptional activity in ehrlich lettré ascites cells through a mechanism involving p38 mitogen-activated protein kinase

Long‐term osmotic stress results in altered gene transcription, however, with the exception of the TonE/TonEBP system, the underlying mechanisms are poorly understood. We previously showed that upon osmotic shrinkage of Ehrlich Lettré Ascites (ELA) fibroblasts, the MEK1‐ERK1/2 pathway is transiently...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of cellular physiology Jg. 226; H. 11; S. 2857 - 2868
Hauptverfasser: Gorbatenko, Andrej, Wiwel, Maria, Klingberg, Henrik, Nielsen, Anni Bech, Kapus, András, Pedersen, Stine Falsig
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.11.2011
Schlagworte:
Animals
Apoptosis
Cell Proliferation
Cells, Cultured
Cyclic AMP Response Element-Binding Protein - metabolism
Mice
Mitogen-Activated Protein Kinase 3 - metabolism
Osmotic Pressure - physiology
p38 Mitogen-Activated Protein Kinases - metabolism
Phosphorylation
Ribosomal Protein S6 Kinases - metabolism
Serine - metabolism
Serum Response Factor - metabolism
Stress, Physiological - physiology
Transcription, Genetic - physiology
ISSN:0021-9541, 1097-4652, 1097-4652
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Long‐term osmotic stress results in altered gene transcription, however, with the exception of the TonE/TonEBP system, the underlying mechanisms are poorly understood. We previously showed that upon osmotic shrinkage of Ehrlich Lettré Ascites (ELA) fibroblasts, the MEK1‐ERK1/2 pathway is transiently inhibited while p38 MAPK is activated, in turn impacting on cell survival (Pedersen et al., 2007, Cell Physiol Biochem 20: 735–750). Here, we show that downstream of these kinases, two transcription factors with major roles in control of cell proliferation and death, serum response factor (SRF) and cAMP response element‐binding protein (CREB) are differentially regulated in ELA cells. SRF Ser103 phosphorylation and SRF‐dependent transcriptional activity were strongly augmented 5–30 min and 24 h, respectively, after hyperosmotic stress (50% increase in extracellular ionic strength), in a p38 MAPK‐dependent manner. In contrast, CREB Ser133 was transiently dephosphorylated upon osmotic shrinkage. The ERK1/2 effector ribosomal S kinase (RSK) and the ERK1/2‐ and p38 MAPK effector mitogen‐ stress‐activated protein kinase 1 (MSK1) both phosphorylate CREB at Ser133. RSK and MSK1 were dephosphorylated within 5 min of shrinkage. MSK1 phosphorylation recovered within 30 min in a p38‐MAPK‐dependent manner. CREB was transiently dephosphorylated after shrinkage in a manner exacerbated by p38 MAPK inhibition or MSK1 knockdown, but unaffected by inhibition of RSK. In conclusion, in ELA cells, hyperosmotic stress activates SRF in a p38 MAPK‐dependent manner and transiently inactivates CREB, likely due to MSK1 inactivation. We suggest that these events contribute to shrinkage‐induced changes in gene transcription and death/survival balance. J. Cell. Physiol. 226: 2857–2868, 2011. © 2011 Wiley‐Liss, Inc.
Bibliographie:The Carlsberg Foundation - No. 2007-01-0663
Canadian Institutes of Health Research - No. MOP 86535
Danish Research Council - No. 272-07-0530
Natural Sciences & Engineering Council of Canada - No. 227908
ArticleID:JCP22628
ark:/67375/WNG-NC2GKPC5-V
istex:DCC03780BE3990DFAD14600EBA30A7D9AC4480EB
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0021-9541
1097-4652
1097-4652
DOI:10.1002/jcp.22628