In:
Cell Communication and Signaling, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2012-12)
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.
Type of Medium:
Online Resource
ISSN:
1478-811X
DOI:
10.1186/1478-811X-10-6
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2012
detail.hit.zdb_id:
2126315-2
SSG:
12
