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@ARTICLE{Niediek:21272,
author = {Niediek, V. and Born, S. and Hampe, N. and Kirchgeßne, N.
and Merkel, R. and Hoffmann, B.},
title = {{C}yclic {S}tretch induces reorientation of cells in a
{S}rc family kinase and p130{C}as dependent manner},
journal = {European Journal of Cell Biology},
volume = {91},
issn = {1618-1298},
address = {München},
publisher = {Elsevier},
reportid = {PreJuSER-21272},
pages = {118 - 128},
year = {2012},
note = {Record converted from VDB: 12.11.2012},
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.},
keywords = {Animals / Cell Movement / Cells, Cultured / Crk-Associated
Substrate Protein: genetics / Crk-Associated Substrate
Protein: metabolism / Fibroblasts: drug effects /
Fibroblasts: physiology / Focal Adhesions / Gene Knockout
Techniques / Mechanotransduction, Cellular / Mice /
Phosphorylation / Proto-Oncogene Proteins c-fyn: genetics /
Proto-Oncogene Proteins c-yes: genetics / Pyrazoles:
pharmacology / Pyrimidines: pharmacology / RNA, Small
Interfering: genetics / Stress, Mechanical / Transfection /
src-Family Kinases: antagonists $\&$ inhibitors / src-Family
Kinases: genetics / src-Family Kinases: metabolism /
4-amino-7-phenylpyrazol(3,4-d)pyrimidine (NLM Chemicals) /
AG 1879 (NLM Chemicals) / Crk-Associated Substrate Protein
(NLM Chemicals) / Pyrazoles (NLM Chemicals) / Pyrimidines
(NLM Chemicals) / RNA, Small Interfering (NLM Chemicals) /
Proto-Oncogene Proteins c-yes (NLM Chemicals) / Fyn protein,
mouse (NLM Chemicals) / Proto-Oncogene Proteins c-fyn (NLM
Chemicals) / Yes1 protein, mouse (NLM Chemicals) /
src-Family Kinases (NLM Chemicals) / J (WoSType)},
cin = {ICS-7},
ddc = {570},
cid = {I:(DE-Juel1)ICS-7-20110106},
pnm = {BioSoft: Makromolekulare Systeme und biologische
Informationsverarbeitung},
pid = {G:(DE-Juel1)FUEK505},
shelfmark = {Cell Biology},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:22178114},
UT = {WOS:000301095900003},
doi = {10.1016/j.ejcb.2011.10.003},
url = {https://juser.fz-juelich.de/record/21272},
}