Three‐dimensional matrix induces sustained activation of ERK1/2 via Src/Ras/Raf signaling pathway

Cell Biology International - Tập 32 - Trang 229-234 - 2008
Ralica Damianova1, Nadezhda Stefanova1, Edna Cukierman2, Albena Momchilova3, Roumen Pankov1
1Department of Cytology, Histology and Embryology, Biological Faculty, Sofia University “St. Kliment Ohridski”, 1164 Sofia, Bulgaria
2Division of Basic Science, Tumor Cell Biology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
3Institute of Biophysics, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria

Tóm tắt

AbstractResearch in cell signaling often depends on tissue culture, but the artificial substrates used to grow cells in vitro are likely to distort the conclusions, particularly when adhesion‐mediated signaling events are investigated. Studies of signal transduction pathways operating in cells grown in three‐dimensional (3D) matrices provide a better system, giving a closer insight of the cell signaling in vivo. We compared the steady‐state levels of ERK1/2 activity in primary human fibroblasts, induced by cell‐derived 3D fibronectin matrix or fibronectin, coated on flat surfaces. 3D environment caused ERK1/2 stimulation concomitant with a 2.5‐fold increase in Ras GTP loading and Src activation. Under these conditions FAK autophosphorylation was suppressed. Treatment with Src inhibitor PP2 abolished these effects indicating that 3D fibronectin matrix activated ERK1/2 through Src/Ras/Raf pathway, bypassing FAK. These observations suggest that within in vivo‐like conditions Src may have a leading role in the induction of sustained ERK1/2 activation.

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Cell Biology International

Tập 32

229-234

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