A signaling pathway from the alpha5beta1 and alpha(v)beta3 integrins that elevates bcl-2 transcription. Export

@article{citeulike:903720, abstract = {Integrin-mediated cell adhesion is necessary for the survival of many cell types, and loss of adhesion causes apoptosis. We have previously shown that the alpha5beta1 integrin supports cell survival on fibronectin and increases Bcl-2 protein expression. Here we show that bcl-2 transcription is elevated in cells that attach to fibronectin through alpha(v)beta1 or to vitronectin through alpha(v)beta3 but is not elevated in cells attaching through the alpha(v)beta1 integrin. Bcl-2 protein expression and protection from apoptosis under serum-free conditions correlated with bcl-2 transcription. This integrin-mediated regulation of bcl-2 is Shc- and FAK-dependent, and activation of Ras by FAK is required. Furthermore, Ras mediates this up-regulation of bcl-2 by activating the phosphatidylinositol 3-kinase-AKT pathway. Mitogen-activated protein kinase did not appear to be necessary for the activation of bcl-2 transcription. Therefore, our work characterizes the pathway that mediates the effect of integrins on bcl-2 transcription and cell survival.}, address = {Cancer Research Center, The Burnham Institute, La Jolla, California 92037, USA.}, author = {Matter, M. L. and Ruoslahti, E.}, citeulike-article-id = {903720}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M102014200}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/11333270}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=11333270}, day = {27}, doi = {10.1074/jbc.M102014200}, issn = {0021-9258}, journal = {J Biol Chem}, keywords = {akt, anoikis, apoptosis, bcl2, fak, integrin, pi3k, shc}, month = {July}, number = {30}, pages = {27757--27763}, posted-at = {2006-10-18 14:49:56}, priority = {3}, title = {A signaling pathway from the alpha5beta1 and alpha(v)beta3 integrins that elevates bcl-2 transcription.}, url = {http://dx.doi.org/10.1074/jbc.M102014200}, volume = {276}, year = {2001} }

TY - JOUR ID - citeulike:903720 L3 - citeulike-article-id:903720 N2 - Integrin-mediated cell adhesion is necessary for the survival of many cell types, and loss of adhesion causes apoptosis. We have previously shown that the alpha5beta1 integrin supports cell survival on fibronectin and increases Bcl-2 protein expression. Here we show that bcl-2 transcription is elevated in cells that attach to fibronectin through alpha(v)beta1 or to vitronectin through alpha(v)beta3 but is not elevated in cells attaching through the alpha(v)beta1 integrin. Bcl-2 protein expression and protection from apoptosis under serum-free conditions correlated with bcl-2 transcription. This integrin-mediated regulation of bcl-2 is Shc- and FAK-dependent, and activation of Ras by FAK is required. Furthermore, Ras mediates this up-regulation of bcl-2 by activating the phosphatidylinositol 3-kinase-AKT pathway. Mitogen-activated protein kinase did not appear to be necessary for the activation of bcl-2 transcription. Therefore, our work characterizes the pathway that mediates the effect of integrins on bcl-2 transcription and cell survival. IS - 30 JF - J Biol Chem SN - 0021-9258 AD - Cancer Research Center, The Burnham Institute, La Jolla, California 92037, USA. EP - 27763 TI - A signaling pathway from the alpha5beta1 and alpha(v)beta3 integrins that elevates bcl-2 transcription. VL - 276 SP - 27757 KW - akt KW - anoikis KW - apoptosis KW - bcl2 KW - fak KW - integrin KW - pi3k KW - shc AU - Matter, ML AU - Ruoslahti, E PY - 2001/07/27/ UR - http://dx.doi.org/10.1074/jbc.M102014200 ER -