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Protein kinase C-δ regulates thrombin-induced ICAM-1 gene expression in endothelial cells via activation of p38 mitogen-activated protein kinase
Rahman A.; Anwar K.N.; Uddin S.; Xu N.; Ye R.D.; Platanias L.C.; Malik A.B.
2001-08-14
Source PublicationMolecular and Cellular Biology
ISSN02707306
Volume21Issue:16Pages:5554-5565
AbstractThe procoagulant thrombin promotes the adhesion of polymorphonuclear leukocytes to endothelial cells by a mechanism involving expression of intercellular adhesion molecule 1 (ICAM-1) via an NF-κB-dependent pathway. We now provide evidence that protein kinase C-δ (PKC-δ) and the p38 mitogen-activated protein (MAP) kinase pathway play a critical role in the mechanism of thrombin-induced ICAM-1 gene expression in endothelial cells. We observed the phosphorylation of PKC-δ and p38 MAP kinase within 1 min after thrombin challenge of human umbilical vein endothelial cells. Pretreatment of these cells with the PKC-δ inhibitor rottlerin prevented the thrombin-induced phosphorylation of p38 MAP kinase, suggesting that p38 MAP kinase signals downstream of PKC-δ. Inhibition of PKC-δ or p38 MAP kinase by pharmacological and genetic approaches markedly decreased the thrombin-induced NF-κB activity and resultant ICAM-1 expression. The effects of PKC-δ inhibition were secondary to inhibition of 1KKβ activation and of subsequent NF-κB binding to the ICAM-1 promoter. The effects of p38 MAP kinase inhibition occurred downstream of IκBα degradation without affecting the DNA binding function of nuclear NF-κB. Thus, PKC-δ signals thrombin-induced ICAM-1 gene transcription by a dual mechanism involving activation of IKIKβ, which mediates NF-κB binding to the ICAM-1 promoter, and p38 MAP kinase, which enhances transactivation potential of the bound NF-κB p65 (RelA).
DOI10.1128/MCB.21.16.5554-5565.2001
URLView the original
Language英語
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Cited Times [WOS]:137   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionPersonal research not belonging to the institution
AffiliationUniversity of Illinois College of Medicine
Recommended Citation
GB/T 7714
Rahman A.,Anwar K.N.,Uddin S.,et al. Protein kinase C-δ regulates thrombin-induced ICAM-1 gene expression in endothelial cells via activation of p38 mitogen-activated protein kinase[J]. Molecular and Cellular Biology,2001,21(16):5554-5565.
APA Rahman A..,Anwar K.N..,Uddin S..,Xu N..,Ye R.D..,...&Malik A.B..(2001).Protein kinase C-δ regulates thrombin-induced ICAM-1 gene expression in endothelial cells via activation of p38 mitogen-activated protein kinase.Molecular and Cellular Biology,21(16),5554-5565.
MLA Rahman A.,et al."Protein kinase C-δ regulates thrombin-induced ICAM-1 gene expression in endothelial cells via activation of p38 mitogen-activated protein kinase".Molecular and Cellular Biology 21.16(2001):5554-5565.
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