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Three‐dimensional matrix induces sustained activation of ERK1/2 via Src/Ras/Raf signaling pathway
Author(s) -
Damianova Ralica,
Stefanova Nadezhda,
Cukierman Edna,
Momchilova Albena,
Pankov Roumen
Publication year - 2008
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1016/j.cellbi.2007.08.029
Subject(s) - fibronectin , microbiology and biotechnology , proto oncogene tyrosine protein kinase src , signal transduction , focal adhesion , autophosphorylation , matrix (chemical analysis) , chemistry , extracellular matrix , biology , phosphorylation , protein kinase a , chromatography
Research 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.