scholarly journals Phosphoinositide 3-kinase (PI3K); HER2 (EGFR2; ERBB2; neu); epidermal growth factor receptor 3 (EGFR3; HER3; ERBB3)

2011 ◽  
Vol 4 (11) ◽  
pp. 304-304
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Epidermal Growth ◽  
Phosphoinositide 3 Kinase

scholarly journals A Dual Phosphoinositide-3-Kinase α/mTOR Inhibitor Cooperates with Blockade of Epidermal Growth Factor Receptor in PTEN-Mutant Glioma

2007 ◽  
Vol 67 (17) ◽  
pp. 7960-7965 ◽  
Author(s):  
Qi-Wen Fan ◽  
Christine K. Cheng ◽  
Theodore P. Nicolaides ◽  
Christopher S. Hackett ◽  
Zachary A. Knight ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Mtor Inhibitor ◽  
Growth Factor Receptor ◽  
Epidermal Growth ◽  
Phosphoinositide 3 Kinase

scholarly journals 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

2007 ◽  
Vol 28 (2) ◽  
pp. 587-600 ◽  
Author(s):  
Carla Sampaio ◽  
Marie Dance ◽  
Alexandra Montagner ◽  
Thomas Edouard ◽  
Nicole Malet ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Signal Strength ◽  
Extracellular Signal Regulated Kinase ◽  
Egfr Activation ◽  
Extracellular Signal ◽  
Epidermal Growth ◽  
Phosphoinositide 3 Kinase

ABSTRACT 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 upon strong epidermal growth factor receptor (EGFR) stimulation and dependent on PI3K upon limited EGFR activation. Using Gab1 mutants, we observed that this conditional role of PI3K is dictated by the EGFR capability of recruiting Gab1 through Grb2 or through the PI3K lipid product PIP3, according to a high or weak level of receptor stimulation, respectively. In agreement, Grb2 siRNA generates, in cells with maximal EGFR stimulation, a strong dependence on PI3K for both Gab1/Shp2 and ERK1-2 activation. Therefore, Ras/ERK1-2 depends on PI3K only when PIP3 is required to recruit Gab1/Shp2, which occurs only under weak EGFR mobilization. Finally, we show that, in glioblastoma cells displaying residual EGFR activation, this compensatory mechanism becomes necessary to efficiently activate ERK1-2, which could probably contribute to tumor resistance to EGFR inhibitors.

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