Signal strength dictates phosphoinositide 3-kinase contribution to Ras/extracellular signal-regulated kinase 1 and 2 activation via differential Gab1/Shp2 recruitment: consequences for resistance to epidermal growth factor receptor inhibition.

@article{Sampaio2008SignalSD,
  title={Signal strength dictates phosphoinositide 3-kinase contribution to Ras/extracellular signal-regulated kinase 1 and 2 activation via differential Gab1/Shp2 recruitment: consequences for resistance to epidermal growth factor receptor inhibition.},
  author={Carla Sampaio and Marie Dance and Alexandra Montagner and Thomas Edouard and Nicole Malet and Bertrand Perret and Armelle Yart and J Y Salles and Patrick Raynal},
  journal={Molecular and cellular biology},
  year={2008},
  volume={28 2},
  pages={587-600}
}
Phosphoinositide 3-kinase (PI3K) participates in extracellular signal-regulated kinase 1 and 2 (ERK1-2) activation according to signal strength, through unknown mechanisms. We report herein that Gab1/Shp2 constitutes a PI3K-dependent checkpoint of ERK1-2 activation regulated according to signal intensity. Indeed, by up- and down-regulation of signal strength in different cell lines and through different methods, we observed that Gab1/Shp2 and Ras/ERK1-2 in concert become independent of PI3K… CONTINUE READING

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