Mechanical stress-activated PKCdelta regulates smooth muscle cell migration.
Vascular smooth muscle cells (SMCs) are exposed to altered mechanical stress that may contribute to SMC migration in the development of atherosclerosis. Signal transduction pathways in SMCs activated by mechanical stress that instigate cell migration are undefined. Herein, we provide evidence that mechanical stress enhances SMC migration, which is mediated, at least in part, by protein kinase C (PKC)delta. When rat SMCs cultivated on a flexible membrane were subjected to cyclic strain stress (60 cycles/min, 5, 15, or 20% elongation), PKCdelta was translocated to the Triton-insoluble fraction, whereas PKCalpha was translocated to the membrane, which was confirmed by PKC kinase assays. Immunofluorescence and actin staining revealed a cytoskeleton translocation of PKCdelta in SMCs stimulated by cyclic strain. PKCdelta-deficient SMCs cultivated from PKCdelta-/- mice showed an abnormal cytoskeleton structure, which was related to a diminished phosphorylation of paxillin, focal adhesion kinase, and vinculin in response to mechanical stress. Mechanical stress enhanced SMC migration, which was diminished in PKCdelta-/- SMCs. Taken together, our data demonstrated that mechanical stress activates PKCdelta translocation to the cytoskeleton, which is related to decreased SMC migration and indicates that PKCdelta is a key signal transducer between mechanical stress and cell migration.
Li
Chaohong
C
Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria.
Wernig
Florian
F
Leitges
Michael
M
Hu
Yanhua
Y
Xu
Qingbo
Q
D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000648:ultrastructure; D004789:Enzyme Activation; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000201:enzymology* / Q000502:physiology* / Q000648:ultrastructure; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D021381:Protein Transport; D051381:Rats; D013314:Stress, Mechanical
C497259:Prkcd protein, mouse; C497260:Prkcd protein, rat; C496630:Prkca protein, mouse; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta