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FEBS Lett. 1999 Feb 5;444(1):71-4.

Raf-1 is activated by the p38 mitogen-activated protein kinase inhibitor, SB203580.

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1
Department of Surgery, University of Washington, Seattle 98195-6410, USA. kalmes@u.washington.edu

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.

PMID:
10037150
DOI:
10.1016/s0014-5793(99)00034-4
[Indexed for MEDLINE]
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