Abstract:
:SB203580 (4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imi dazole) is widely used as a specific inhibitor of p38 mitogen-activated protein kinase (MAPK). Here, we report that SB203580 activates the serine/threonine kinase Raf-1 in quiescent smooth muscle cells in a dose-dependent fashion. The concentrations of SB203580 required lie above those necessary to inhibit p38 MAPK and we were unable to detect basal levels of active p38 MAPK. SB203580 does not directly activate Raf-1 in vitro, and fails to activate Ras, MEK, and ERK in intact cells. In vitro, however, SB203580-stimulated Raf-1 activates MEK1 in a coupled assay. We conclude that activation of Raf-1 by SB203580 is not mediated by an inhibition of p38 MAPK, is Ras-independent, and is uncoupled from MEK/ERK signaling.
journal_name
FEBS Lettjournal_title
FEBS lettersauthors
Kalmes A,Deou J,Clowes AW,Daum Gdoi
10.1016/s0014-5793(99)00034-4keywords:
subject
Has Abstractpub_date
1999-02-05 00:00:00pages
71-4issue
1eissn
0014-5793issn
1873-3468pii
S0014-5793(99)00034-4journal_volume
444pub_type
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