17 VASCULAR CELL ADHESION MOLECULE 1 ACTIVATION OF ENDOTHELIAL PROTEIN KINASE C α. (1st March 2007)

• Record Type: Journal Article
• Authors: Abdala-Valencia, H.; Cook-Mills, J. M.
• Is Part Of: Journal of investigative medicine. Volume 55:Number 2(2007)
• Page Start: S350
• Page End: S350
• Publication Date: 2007-03-01
• Subjects: Clinical medicine -- Periodicals; Medicine -- Research -- Periodicals; Medicine; Research -- United States; Clinical medicine; Medicine -- Research; Periodicals; 616.075
• DOI: 10.1136/jim-55-02-17
• Languages: English
• ISSNs: 1081-5589

Abstract

Abstract : Lymphocyte binding to vascular cell adhesion molecule 1 (VCAM-1) activates endothelial cell NADPH oxidase, resulting in the generation of 1 μM of hydrogen peroxide. This is required for VCAM-1-dependent lymphocyte migration. In this report, we identified a role for protein kinase Cα (PKCα) in VCAM-1 signal transduction in human and mouse endothelial cells. VCAM-1-dependent lymphocyte migration under 2 dynes/cm 2 laminar flow was blocked by pretreatment of endothelial cells with dominant negative PKCα or the PKCα-selective inhibitors, Rö-32-0432 or Gö-6976. Phosphorylation of PKCαThr638, an autophosphorylation site indicating enzyme activity, was increased by antibody crosslinking of VCAM-1 on endothelial cells or by the exogenous addition of 1 μM of hydrogen peroxide. The anti-VCAM-1-stimulated phosphorylation of PKCαThr638 was blocked by scavenging of hydrogen peroxide and by inhibition of NADPH oxidase. Furthermore, anti-VCAM-1 signaling induced the oxidation of PKCα. Oxidized PKCα is a transiently active form of PKCα that is diacylglycerol independent. This oxidation was blocked by inhibition of NADPH oxidase. In summary, VCAM-1 activation of endothelial cell NADPH oxidase induces transient PKCα activation that is necessary for VCAM-1-dependent transendothelial lymphocyte migration.