TY  - JOUR
AU  - Niediek, V.
AU  - Born, S.
AU  - Hampe, N.
AU  - Kirchgeßne, N.
AU  - Merkel, R.
AU  - Hoffmann, B.
TI  - Cyclic Stretch induces reorientation of cells in a Src family kinase and p130Cas dependent manner
JO  - European Journal of Cell Biology
VL  - 91
SN  - 1618-1298
CY  - München
PB  - Elsevier
M1  - PreJuSER-21272
SP  - 118 - 128
PY  - 2012
N1  - Record converted from VDB: 12.11.2012
AB  - 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.
KW  - Animals
KW  - Cell Movement
KW  - Cells, Cultured
KW  - Crk-Associated Substrate Protein: genetics
KW  - Crk-Associated Substrate Protein: metabolism
KW  - Fibroblasts: drug effects
KW  - Fibroblasts: physiology
KW  - Focal Adhesions
KW  - Gene Knockout Techniques
KW  - Mechanotransduction, Cellular
KW  - Mice
KW  - Phosphorylation
KW  - Proto-Oncogene Proteins c-fyn: genetics
KW  - Proto-Oncogene Proteins c-yes: genetics
KW  - Pyrazoles: pharmacology
KW  - Pyrimidines: pharmacology
KW  - RNA, Small Interfering: genetics
KW  - Stress, Mechanical
KW  - Transfection
KW  - src-Family Kinases: antagonists & inhibitors
KW  - src-Family Kinases: genetics
KW  - src-Family Kinases: metabolism
KW  - 4-amino-7-phenylpyrazol(3,4-d)pyrimidine (NLM Chemicals)
KW  - AG 1879 (NLM Chemicals)
KW  - Crk-Associated Substrate Protein (NLM Chemicals)
KW  - Pyrazoles (NLM Chemicals)
KW  - Pyrimidines (NLM Chemicals)
KW  - RNA, Small Interfering (NLM Chemicals)
KW  - Proto-Oncogene Proteins c-yes (NLM Chemicals)
KW  - Fyn protein, mouse (NLM Chemicals)
KW  - Proto-Oncogene Proteins c-fyn (NLM Chemicals)
KW  - Yes1 protein, mouse (NLM Chemicals)
KW  - src-Family Kinases (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:22178114
UR  - <Go to ISI:>//WOS:000301095900003
DO  - DOI:10.1016/j.ejcb.2011.10.003
UR  - https://juser.fz-juelich.de/record/21272
ER  -