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000021272 0247_ $$2DOI$$a10.1016/j.ejcb.2011.10.003
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000021272 084__ $$2WoS$$aCell Biology
000021272 1001_ $$0P:(DE-Juel1)VDB84258$$aNiediek, V.$$b0$$uFZJ
000021272 245__ $$aCyclic Stretch induces reorientation of cells in a Src family kinase and p130Cas dependent manner
000021272 260__ $$aMünchen$$bElsevier$$c2012
000021272 300__ $$a118 - 128
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000021272 440_0 $$016741$$aEuropean Journal of Cell Biology$$v91$$x1618-1298$$y2
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000021272 520__ $$aRecognition of external mechanical signals by cells is an essential process for life. One important mechanical signal experienced by various cell types, e.g. around blood vessels, within the lung epithelia or around the intestine, is cyclic stretch. As a response, many cell types reorient their actin cytoskeleton and main cell axis almost perpendicular to the direction of stretch. Despite the vital necessity of cellular adaptation to cyclic stretch, the underlying mechanosensory signal cascades are far from being understood. Here we show an important function of Src-family kinase activity in cellular reorientation upon cyclic stretch. Deletion of all three family members, namely c-Src, Yes and Fyn (SYF), results in a strongly impaired cell reorientation of mouse embryonic fibroblasts with an only incomplete reorientation upon expression of c-Src. We further demonstrate that this reorientation phenotype of SYF-depleted cells is not caused by affected protein exchange dynamics within focal adhesions or altered cell force generation. Instead, Src-family kinases regulate the reorientation in a mechanotransduction-dependent manner, since knock-down and knock-out of p130Cas, a putative stretch sensor known to be phosphorylated by Src-family kinases, also reduce cellular reorientation upon cyclic stretch. This impaired reorientation is identical in intensity upon mutating stretch-sensitive tyrosines of p130Cas only. These statistically highly significant data pinpoint early events in a Src family kinase- and p130Cas-dependent mechanosensory/mechanotransduction pathway.
000021272 536__ $$0G:(DE-Juel1)FUEK505$$2G:(DE-HGF)$$aBioSoft: Makromolekulare Systeme und biologische Informationsverarbeitung$$cP45$$x0
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000021272 650_2 $$2MeSH$$aAnimals
000021272 650_2 $$2MeSH$$aCell Movement
000021272 650_2 $$2MeSH$$aCells, Cultured
000021272 650_2 $$2MeSH$$aCrk-Associated Substrate Protein: genetics
000021272 650_2 $$2MeSH$$aCrk-Associated Substrate Protein: metabolism
000021272 650_2 $$2MeSH$$aFibroblasts: drug effects
000021272 650_2 $$2MeSH$$aFibroblasts: physiology
000021272 650_2 $$2MeSH$$aFocal Adhesions
000021272 650_2 $$2MeSH$$aGene Knockout Techniques
000021272 650_2 $$2MeSH$$aMechanotransduction, Cellular
000021272 650_2 $$2MeSH$$aMice
000021272 650_2 $$2MeSH$$aPhosphorylation
000021272 650_2 $$2MeSH$$aProto-Oncogene Proteins c-fyn: genetics
000021272 650_2 $$2MeSH$$aProto-Oncogene Proteins c-yes: genetics
000021272 650_2 $$2MeSH$$aPyrazoles: pharmacology
000021272 650_2 $$2MeSH$$aPyrimidines: pharmacology
000021272 650_2 $$2MeSH$$aRNA, Small Interfering: genetics
000021272 650_2 $$2MeSH$$aStress, Mechanical
000021272 650_2 $$2MeSH$$aTransfection
000021272 650_2 $$2MeSH$$asrc-Family Kinases: antagonists & inhibitors
000021272 650_2 $$2MeSH$$asrc-Family Kinases: genetics
000021272 650_2 $$2MeSH$$asrc-Family Kinases: metabolism
000021272 650_7 $$00$$2NLM Chemicals$$a4-amino-7-phenylpyrazol(3,4-d)pyrimidine
000021272 650_7 $$00$$2NLM Chemicals$$aAG 1879
000021272 650_7 $$00$$2NLM Chemicals$$aCrk-Associated Substrate Protein
000021272 650_7 $$00$$2NLM Chemicals$$aPyrazoles
000021272 650_7 $$00$$2NLM Chemicals$$aPyrimidines
000021272 650_7 $$00$$2NLM Chemicals$$aRNA, Small Interfering
000021272 650_7 $$0EC 2.7.10.1$$2NLM Chemicals$$aProto-Oncogene Proteins c-yes
000021272 650_7 $$0EC 2.7.10.2$$2NLM Chemicals$$aFyn protein, mouse
000021272 650_7 $$0EC 2.7.10.2$$2NLM Chemicals$$aProto-Oncogene Proteins c-fyn
000021272 650_7 $$0EC 2.7.10.2$$2NLM Chemicals$$aYes1 protein, mouse
000021272 650_7 $$0EC 2.7.10.2$$2NLM Chemicals$$asrc-Family Kinases
000021272 650_7 $$2WoSType$$aJ
000021272 65320 $$2Author$$ap130Cas
000021272 65320 $$2Author$$ac-Src
000021272 65320 $$2Author$$aFyn
000021272 65320 $$2Author$$aYes
000021272 65320 $$2Author$$aCyclic stretch
000021272 65320 $$2Author$$aCell reorientation
000021272 65320 $$2Author$$aTyrosine phosphorylation
000021272 65320 $$2Author$$aMechanotransduction
000021272 7001_ $$0P:(DE-Juel1)161241$$aBorn, S.$$b1$$uFZJ
000021272 7001_ $$0P:(DE-Juel1)128813$$aHampe, N.$$b2$$uFZJ
000021272 7001_ $$0P:(DE-Juel1)VDB106792$$aKirchgeßne, N.$$b3$$uFZJ
000021272 7001_ $$0P:(DE-Juel1)128833$$aMerkel, R.$$b4$$uFZJ
000021272 7001_ $$0P:(DE-Juel1)VDB27696$$aHoffmann, B.$$b5$$uFZJ
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000021272 8567_ $$uhttp://dx.doi.org/10.1016/j.ejcb.2011.10.003
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