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

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 Lett

journal_title

FEBS letters

authors

Kalmes A,Deou J,Clowes AW,Daum G

doi

10.1016/s0014-5793(99)00034-4

keywords:

subject

Has Abstract

pub_date

1999-02-05 00:00:00

pages

71-4

issue

1

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(99)00034-4

journal_volume

444

pub_type

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