Depletion of protein kinase N3 (PKN3) impairs actin and adherens junctions dynamics and attenuates endothelial cell activation
- 作者：Kristin Mö ; pert ; Kathrin Lö ; ffler ; Nadine Rö ; der ; Jö ; rg Kaufmann ; Ansgar Santel ; a.santel@silence-therapeutics.com
- 关键词：ICAM-1 ; FAK ; Atu027 ; TNF-伪 activated endothelium ; Inflammation
- 刊名：European Journal of Cell Biology
- 出版年：2012
- 期刊代码：15_01719335
- 类别：bio
- 出版时间：September, 2012
- 卷：91
- 期：9
- 页码：694-705
- 文件大小：3030 K
摘要
Several pathways are involved in the control of endothelial cell morphology, endothelial permeability and function in order to maintain vascular homeostasis. Here we report that protein kinase N3 (PKN3) appears to play a pivotal role in maintaining endothelial cell morphology, cell-cell junctions and motility. An RNAi-based cell biological approach in cultured human endothelial cells (HUVEC) revealed that knockdown of PKN3 expression gave rise to cells with divergent cell morphology, impaired locomotion, disturbed adherens junctions (AJ) integrity and irregular actin organization. Notably, knockdown of PKN3 cells led to improper stress fiber formation and marked adhesiveness of intercellular adherens junctions when cells became stimulated with the pro-inflammatory cytokine TNF-伪. Moreover, TNF-伪-induced ICAM-1 expression on the cell surface was reduced in cells with suppressed PKN3 expression. Finally, loss-of-function for PKN3 appeared to affect Pyk2 phosphorylation in endothelial cells. These observations suggest that PKN3 can be considered a novel protein implicated in remodeling the actin-adherens junction, possibly by linking ICAM-1-signaling with actin/AJ dynamics. We propose that loss of PKN3 function and concomitant aberrations in actin rearrangement may attenuate pro-inflammatory activation of endothelial cells.