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...

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Vydáno v:	Journal of cellular physiology Ročník 226; číslo 11; s. 2857 - 2868
Hlavní autoři:	Gorbatenko, Andrej, Wiwel, Maria, Klingberg, Henrik, Nielsen, Anni Bech, Kapus, András, Pedersen, Stine Falsig
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.11.2011
Témata:	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
On-line přístup:	Získat plný text
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Popis
Shrnutí:	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.
Bibliografie:	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