FCCC LOGO Faculty Publications
Damianova R , Stefanova N , Cukierman E , Momchilova A , Pankov R
Three-dimensional matrix induces sustained activation of ERK1/2 via Src/Ras/Raf signaling pathway
Cell Biology International. 2008 Feb;32(2) :229-234
PMID: ISI:000260586300008   
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Abstract
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. (C) 2007 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.
Notes
ISI Document Delivery No.: 367XQ Times Cited: 1 Cited Reference Count: 41 Cited References: AHLFORS JEW, 2007, BIOMATERIALS, V28, P21 AKIYAMA SK, 1989, J CELL BIOL, V109, P863 AVRUCH J, 1994, TRENDS BIOCHEM SCI, V19, P279 BISSELL MJ, 2001, NAT REV CANCER, V1, P46 BROTT BK, 1991, MOL CELL BIOL, V11, P5059 BROWN MC, 2004, PHYSIOL REV, V84, P1315, DOI 10.1152/physrev.00002.2004 CABODI S, 2004, BIOCHEM SOC T 3, V32, P438 CALALB MB, 1995, MOL CELL BIOL, V15, P954 CUKIERMAN E, 2001, CURR PROTOCOLS CELL CUKIERMAN E, 2001, SCIENCE, V294, P1708 CUKIERMAN E, 2002, CURR OPIN CELL BIOL, V14, P633 DILWORTH SM, 1994, NATURE, V367, P87 EDIN ML, 2005, MOL CELL BIOL, V25, P4466, DOI 10.1128/MCB.25.11.4466-4475.2005 ELLIS C, 1990, NATURE, V343, P377 FRIEDL P, 2004, INT J DEV BIOL, V48, P441 GEIGER B, 2001, NAT REV MOL CELL BIO, V2, P793 GRINNELL F, 2000, TRENDS CELL BIOL, V10, P362 HANKE JH, 1996, J BIOL CHEM, V271, P695 HISA DA, 2005, MOL CELL BIOL, V25, P9700 ISHII I, 2001, ATHEROSCLEROSIS, V158, P377 KLEINMAN HK, 2005, SEMIN CANCER BIOL, V15, P378, DOI 10.1016/j.semcancer.2005.05.004 LEE JW, 2004, MOL CELLS, V17, P188 MARSHALL MS, 1995, FASEB J, V9, P1311 MELOCHE S, 2007, ONCOGENE, V26, P3227, DOI 10.1038/sj.onc.1210414 MITRA SK, 2006, CURR OPIN CELL BIOL, V18, P516, DOI 10.1016/j.ceb.2006.08.011 MORRISON DK, 1997, CURR OPIN CELL BIOL, V9, P174 PANKOV R, 2005, J CELL BIOL, V170, P793, DOI 10.1083/jcb.200503152 PARSONS JT, 2003, J CELL SCI, V116, P1409, DOI 10.1242/jcs.00373 PIZZO AM, 2005, J APPL PHYSIOL, V98, P1909, DOI 10.1152/japplphysiol.01137.2004 ROSKOSKI R, 2005, BIOCHEM BIOPH RES CO, V331, P1, DOI 10.1016/j.bbrc.2005.03.012 ROZAKISADCOCK M, 1992, NATURE, V360, P689 SCHLAEPFER DD, 1997, J BIOL CHEM, V272, P13189 SCHLAEPFER DD, 1998, MOL CELL BIOL, V18, P2571 SHARROCKS AD, 2006, CURR BIOL, V16, R540, DOI 10.1016/j.cub.2006.06.038 SHATTIL SJ, 2005, TRENDS CELL BIOL, V15, P399, DOI 10.1016/j.tcb.2005.06.005 SHI Q, 2003, MOL BIOL CELL, V14, P4306 WOZNIAK MA, 2003, J CELL BIOL, V163, P583, DOI 10.1083/jcb.200305010 YAMADA KM, 2003, BRAZ J MED BIOL RES, V36, P959 ZHANG SQ, 2004, MOL CELL, V13, P341 ZHANG XF, 1993, NATURE, V364, P308 ZHAO JH, 1998, J CELL BIOL, V143, P1997 Damianova, Ralica Stefanova, Nadezhda Cukierman, Edna Momchilova, Albena Pankov, Roumen ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD; 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND