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Differential p38-dependent signalling in response to cellular stress and mitogenic stimulation in fibroblasts

Faust, D.; Schmitt, C.; Oesch, F.; Oesch-Bartlomowicz, B.; Schreck, I. 1; Weiss, C. 1; Dietrich, C.
1 Institut für Toxikologie und Genetik (ITG), Karlsruher Institut für Technologie (KIT)


p38 MAP kinase is known to be activated by cellular stress finally leading to cell cycle arrest or apoptosis. Furthermore, a tumour suppressor role of p38 MAPK has been proposed. In contrast, a requirement of p38 for proliferation has also been described. To clarify this paradox, we investigated stress- and mitogen-induced p38 signalling in the same cell type using fibroblasts. We demonstrate that - in the same cell line - p38 is activated by mitogens or cellular stress, but p38-dependent signalling is different. Exposure to cellular stress, such as anisomycin, leads to a strong and persistent p38 activation independent of GTPases. As a result, MK2 and downstream the transcription factor CREB are phosphorylated. In contrast, mitogenic stimulation results in a weaker and transient p38 activation, which upstream involves small GTPases and is required for cyclin D1 induction. Consequently, the retinoblastoma protein is phosphorylated and allows G1/S transition. Our data suggest a dual role of p38 and indicate that the level and/or duration of p38 activation determines the cellular response, i.e either proliferation or cell cycle arrest.

Verlagsausgabe §
DOI: 10.5445/IR/110089699
DOI: 10.1186/1478-811X-10-6
Zitationen: 49
Zitationen: 51
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Toxikologie und Genetik (ITG)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2012
Sprache Englisch
Identifikator ISSN: 1478-811X
KITopen-ID: 110089699
HGF-Programm 47.01.01 (POF II, LK 01) Biologische Schlüselmoleküle ITG
Erschienen in Cell communication and signaling
Verlag Springer Fachmedien Wiesbaden
Band 10
Seiten 6
Schlagwörter p38 MAPK, Signalling, Cellular stress, Mitogens, Fibroblasts
Nachgewiesen in Dimensions
Web of Science
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