Referenced in: none

Automatically associated channels: Kv12.1 , Slo1

Title: Sequential activation of protein kinase C (PKC)-alpha and PKC-epsilon contributes to sustained Raf/ERK1/2 activation in endothelial cells under mechanical strain.

Authors: J J Cheng, B S Wung, Y J Chao, D L Wang

Journal, date & volume: J. Biol. Chem., 2001 Aug 17 , 276, 31368-75

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/11399752

Abstract
Endothelial cells (ECs) are constantly subjected to hemodynamic forces including cyclic pressure-induced strain. The role of protein kinase C (PKC) in cyclic strain-treated ECs was studied. PKC activities were induced as cyclic strain was initiated. Cyclic strain to ECs caused activation of PKC-alpha and -epsilon. The translocation of PKC-alpha and -epsilon but not PKC-beta from the cytosolic to membrane fraction was observed. An early transient activation of PKC-alpha versus a late but sustained activation of PKC-epsilon was shown after the onset of cyclic strain. Consistently, a sequential association of PKC-alpha and -epsilon with the signaling molecule Raf-1 was shown. ECs treated with a PKC inhibitor (calphostin C) abolished the cyclic strain-induced Raf-1 activation. ECs under cyclic strain induced a sustained activation of extracellular signal-regulated protein kinases (ERK1/2), which was inhibited by treating ECs with calphostin C. ECs treated with a specific Ca(2+)-dependent PKC inhibitor (Go 6976) showed an inhibition in the early phase of ERK1/2 activation but not in the late and sustained phase. ECs transfected with the antisense to PKC-alpha, the antisense to PKC-epsilon, or the inhibition peptide to PKC-epsilon reduced strain-induced ERK1/2 phosphorylation in a temporal manner. PKC-alpha mediated mainly the early ERK1/2 activation, whereas PKC-epsilon was involved in the sustained ERK1/2 activation. Strained ECs increased transcriptional activity of Elk1 (an ERK1/2 substrate). ECs transfected with the antisense to each PKC isoform reduced Elk1 and monocyte chemotactic protein-1 promotor activity. Our findings conclude that a sequential activation of PKC isoform (alpha and epsilon) contribute to Raf/ERK1/2 activation, and PKC-epsilon appears to play a key role in endothelial adaptation to hemodynamic environment.