KIT | KIT-Bibliothek | Impressum | Datenschutz

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)

Abstract:

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
Veröffentlicht am 09.05.2018
Originalveröffentlichung
DOI: 10.1186/1478-811X-10-6
Scopus
Zitationen: 49
Web of Science
Zitationen: 46
Dimensions
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
urn:nbn:de:swb:90-AAA1100896991
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
Scopus
KIT – Die Forschungsuniversität in der Helmholtz-Gemeinschaft
KITopen Landing Page