Uni-axial cyclic stretch induces c-src activation and translocation in human endothelial cells via SA channel activation.
The kinase activity of c-src increased and peaked at 15 min after an application of uni-axial cyclic stretch in HUVECs followed by a translocation of c-src to Triton-insoluble fraction. Suppression of c-src by an antisense S-oligodeoxynucleotide inhibited the stretch-induced tyrosine phosphorylation and morphological changes. The stretch-induced increase in c-src activity was inhibited by FK506, a specific inhibitor for calcineurin, by Gd3+, a blocker for stretch activated channels, and by the extracellular Ca2+ depletion suggesting the involvement of SA channels. These results strongly suggest c-src plays an important role in the downstream of SA channel activation followed by the morphological changes.
Naruse
K
K
Department of Physiology, Nagoya University School of Medicine, Japan. knaruse@tsuru.med.nagoya-u.ac.jp
Sai
X
X
Yokoyama
N
N
Sokabe
M
M
D065095:Calcineurin Inhibitors; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005682:Gadolinium / Q000494:pharmacology; D005786:Gene Expression Regulation; D016391:Genes, src; D006801:Humans; D007700:Kinetics; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D019000:Phosphotyrosine / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000096:biosynthesis / Q000235:genetics*; D013314:Stress, Mechanical; D016559:Tacrolimus / Q000494:pharmacology; D014471:Umbilical Veins
D065095:Calcineurin Inhibitors; D015220:Calcium Channels; D016376:Oligonucleotides, Antisense; D019000:Phosphotyrosine; D005682:Gadolinium; D016392:Proto-Oncogene Proteins pp60(c-src); D016559:Tacrolimus