MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rahman, A.
Right arrow Articles by Malik, A. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rahman, A.
Right arrow Articles by Malik, A. B.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 2001, p. 5554-5565, Vol. 21, No. 16
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.16.5554-5565.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Protein Kinase C-delta Regulates Thrombin-Induced ICAM-1 Gene Expression in Endothelial Cells via Activation of p38 Mitogen-Activated Protein Kinase

Arshad Rahman,1,* Khandaker N. Anwar,1 Shahab Uddin,2,3 Ning Xu,1 Richard D. Ye,1 Leonidas C. Platanias,2,3 and Asrar B. Malik1

Department of Pharmacology1 and Section of Hematology-Oncology,2 The University of Illinois College of Medicine, Chicago, Illinois 60612, and West Side Veteran Affairs Hospital, Chicago, Illinois 606073

Received 30 October 2000/Returned for modification 16 January 2001/Accepted 25 May 2001

The 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-kappa B-dependent pathway. We now provide evidence that protein kinase C-delta (PKC-delta ) 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-delta and p38 MAP kinase within 1 min after thrombin challenge of human umbilical vein endothelial cells. Pretreatment of these cells with the PKC-delta inhibitor rottlerin prevented the thrombin-induced phosphorylation of p38 MAP kinase, suggesting that p38 MAP kinase signals downstream of PKC-delta . Inhibition of PKC-delta or p38 MAP kinase by pharmacological and genetic approaches markedly decreased the thrombin-induced NF-kappa B activity and resultant ICAM-1 expression. The effects of PKC-delta inhibition were secondary to inhibition of IKKbeta activation and of subsequent NF-kappa B binding to the ICAM-1 promoter. The effects of p38 MAP kinase inhibition occurred downstream of Ikappa Balpha degradation without affecting the DNA binding function of nuclear NF-kappa B. Thus, PKC-delta signals thrombin-induced ICAM-1 gene transcription by a dual mechanism involving activation of IKKbeta , which mediates NF-kappa B binding to the ICAM-1 promoter, and p38 MAP kinase, which enhances transactivation potential of the bound NF-kappa B p65 (RelA).

* Corresponding author. Mailing address: Department of Pharmacology (M/C 868), University of Illinois College of Medicine, 835 South Wolcott Ave., Chicago, IL 60612-7343. Phone: (312) 355-0242. Fax: (312) 413-0222. E-mail: ARahman{at}uic.edu.

Molecular and Cellular Biology, August 2001, p. 5554-5565, Vol. 21, No. 16
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.16.5554-5565.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2001 by the American Society for Microbiology. All rights reserved.