Inhibition of MAP kinase kinase (MEK) blocks endothelial PGI2 release but has no effect on von Willebrand factor secretion or E‐selectin expression

FEBS Letters

Wheeler-Jones, Caroline P.D.¹  May, Michael J.¹  Houliston, Rebecca A.¹  Pearson, Jeremy D.¹ 

[1] Vascular Biology Research Centre, King's College London, Campden Hill Road, Kensington, London W8 7AH, UK

关键词: Human endothelial cell;    MAP kinase;    Thrombin;    Cytokine;    Prostacyclin;    Adhesion molecule;    HUVEC;    human umbilical vein endothelial cell;    MAP kinase;    mitogen activated protein kinase;    MEK;    MAP kinase kinase;    p42mapk;    42 kDa MAP kinase;    p44mapk;    44 kDa MAP kinase;    PGI2;    prostacyclin;    vWF;    von Willebrand Factor;    GPCA;    G protein-coupled agonist;   

DOI  :  10.1016/0014-5793(96)00547-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We have examined the potential role of MAP kinase in the regulation of endothelial cell PGI₂ synthesis, vWF secretion and E-selectin expression using the specific MEK inhibitor PD98059. PD98059 dose-dependently attenuated the tyrosine phosphorylation and activation of p42^mapk in response to thrombin or inflammatory cytokines. Inhibition of thrombin-induced p42^mapk activation was paralleled by an inhibitory effect of PD98059 on thrombin-driven PGI₂ generation but not on vWF secretion or IL-1α/TNFα-induced E-selectin expression. These results provide evidence for a key role for p42^mapk in the acute regulation of PGI₂ synthesis in human endothelial cells and suggest that activation of the MAP kinase cascade is not obligatory for cytokine-stimulated E-selectin expression.

【 授权许可】

Unknown