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

FEBS Letters

Deou, Jessie¹  Daum, Günter¹  Clowes, Alexander W¹  Kalmes, Andreas¹ 

[1] Department of Surgery, University of Washington, 1959 N.E. Pacific St., Seattle, WA 98195-6410, USA

关键词: Ras;    Raf;    Mitogen-activated protein kinase;    SB203580;    Signal transduction;    ECL;    enhanced chemiluminescence;    ERK;    extracellular signal-regulated kinase;    GST;    glutathione S-transferase;    MAPK;    mitogen-activated protein kinase;    MAPKAPK;    MAPK-activated protein kinase;    MEK;    MAPK/ERK kinase;    PDGF;    platelet-derived growth factor;    RBD;    Ras-binding domain of Raf;    SMC;    smooth muscle cell;   

DOI  :  10.1016/S0014-5793(99)00034-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

SB203580 (4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole) 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.

【 授权许可】

Unknown