RRC ID 41892
Author Numazawa S, Watabe M, Nishimura S, Kurosawa M, Izuno M, Yoshida T.
Title Regulation of ERK-mediated signal transduction by p38 MAP kinase in human monocytic THP-1 cells.
Journal J Biochem
Abstract SB 203580 has been widely used to specifically shut down the p38 MAP kinase-dependent pathway, although it is capable of inducing c-Raf kinase activity in cells. The present study demonstrates that SB 203580 activates members of the ERK cascade, c-Raf, MEK, and ERK, in human monocytic THP-1 cells. The activation of these kinases was sustained for at least 24 h after SB 203580 treatment and was also observed in U937 cells, suggesting that c-Raf efficiently transduces the signal even in the presence of the inhibitor in these cells. However, the expression of ERK cascade-dependent genes, such as c-fos and IL-1beta, was extremely limited. Analysis of the cellular distribution of ERK in SB 203580-treated cells indicated that nuclear translocation of phosphorylated ERK was impaired. Also, nuclear translocation of ERK induced by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was inhibited by SB 239063, which does not associate with c-Raf and is highly selective for p38 MAP kinase. In addition, the forced expression of the dominant negative mutant of p38 MAP kinase suppressed serum responsive element-dependent transactivation induced by TPA. These results suggest that the steady-state level of p38 MAP kinase activity modulates ERK signaling.
Volume 133(5)
Pages 599-605
Published 2003-5
DOI 10.1093/jb/mvg077
PMID 12801911
MeSH Animals Biological Transport / drug effects COS Cells Cell Line Cell Nucleus / metabolism Enzyme Activation / drug effects Gene Expression Genes, Reporter / genetics Humans Imidazoles / pharmacology Luciferases / metabolism MAP Kinase Signaling System / physiology* Mitogen-Activated Protein Kinases / genetics Mitogen-Activated Protein Kinases / metabolism* Monocytes / enzymology* Proto-Oncogene Proteins c-raf / metabolism Pyridines / pharmacology Serum Response Element / physiology Transcriptional Activation Transfection p38 Mitogen-Activated Protein Kinases
IF 2.23
Times Cited 19
Human and Animal Cells