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| Hauptseite > Publikationsdatenbank > Cyclic Stretch induces reorientation of cells in a Src family kinase and p130Cas dependent manner |
| Hauptseite > Publikationsdatenbank > Cyclic Stretch induces reorientation of cells in a Src family kinase and p130Cas dependent manner |
| Journal Article | PreJuSER-21272 |
; ; ; ; ;
2012
Elsevier
München
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Please use a persistent id in citations: doi:10.1016/j.ejcb.2011.10.003
Abstract: Recognition of external mechanical signals by cells is an essential process for life. One important mechanical signal experienced by various cell types, e.g. around blood vessels, within the lung epithelia or around the intestine, is cyclic stretch. As a response, many cell types reorient their actin cytoskeleton and main cell axis almost perpendicular to the direction of stretch. Despite the vital necessity of cellular adaptation to cyclic stretch, the underlying mechanosensory signal cascades are far from being understood. Here we show an important function of Src-family kinase activity in cellular reorientation upon cyclic stretch. Deletion of all three family members, namely c-Src, Yes and Fyn (SYF), results in a strongly impaired cell reorientation of mouse embryonic fibroblasts with an only incomplete reorientation upon expression of c-Src. We further demonstrate that this reorientation phenotype of SYF-depleted cells is not caused by affected protein exchange dynamics within focal adhesions or altered cell force generation. Instead, Src-family kinases regulate the reorientation in a mechanotransduction-dependent manner, since knock-down and knock-out of p130Cas, a putative stretch sensor known to be phosphorylated by Src-family kinases, also reduce cellular reorientation upon cyclic stretch. This impaired reorientation is identical in intensity upon mutating stretch-sensitive tyrosines of p130Cas only. These statistically highly significant data pinpoint early events in a Src family kinase- and p130Cas-dependent mechanosensory/mechanotransduction pathway.
Keyword(s): Animals (MeSH) ; Cell Movement (MeSH) ; Cells, Cultured (MeSH) ; Crk-Associated Substrate Protein: genetics (MeSH) ; Crk-Associated Substrate Protein: metabolism (MeSH) ; Fibroblasts: drug effects (MeSH) ; Fibroblasts: physiology (MeSH) ; Focal Adhesions (MeSH) ; Gene Knockout Techniques (MeSH) ; Mechanotransduction, Cellular (MeSH) ; Mice (MeSH) ; Phosphorylation (MeSH) ; Proto-Oncogene Proteins c-fyn: genetics (MeSH) ; Proto-Oncogene Proteins c-yes: genetics (MeSH) ; Pyrazoles: pharmacology (MeSH) ; Pyrimidines: pharmacology (MeSH) ; RNA, Small Interfering: genetics (MeSH) ; Stress, Mechanical (MeSH) ; Transfection (MeSH) ; src-Family Kinases: antagonists & inhibitors (MeSH) ; src-Family Kinases: genetics (MeSH) ; src-Family Kinases: metabolism (MeSH) ; 4-amino-7-phenylpyrazol(3,4-d)pyrimidine ; AG 1879 ; Crk-Associated Substrate Protein ; Pyrazoles ; Pyrimidines ; RNA, Small Interfering ; Proto-Oncogene Proteins c-yes ; Fyn protein, mouse ; Proto-Oncogene Proteins c-fyn ; Yes1 protein, mouse ; src-Family Kinases ; J ; p130Cas (auto) ; c-Src (auto) ; Fyn (auto) ; Yes (auto) ; Cyclic stretch (auto) ; Cell reorientation (auto) ; Tyrosine phosphorylation (auto) ; Mechanotransduction (auto)
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