Reaction: Conversion of PIP2 to PIP3 by PI3K bound to ligand-responsive p-6Y-EGFR mutants
The kinase activity of PI3K mediates the phosphorylation of PIP2 to form PIP3. It is assumed that EGFR cancer mutants induce PI3K/AKT signaling in a manner similar to wild-type EGFR. Phosphorylation of AKT on serine residue S473, and therby activation of PI3K/AKT signaling cascade, has been directly demonstrated in cells expressing the following EGFR cancer mutants: EGFR L858R mutant (Sordella et al. 2004, Paez et al. 2004, Greulich et al. 2005, Shimamura et al. 2005); EGFR G719S mutant (Greulich et al. 2005); EGFR E746_A750del mutant (Sordella et al. 2004, Shimamura et al. 2005); EGFR L747_P753insS mutant (Sordella et al. 2004); EGFR L747_A750delinsP mutant (Greulich et al. 2005); EGFR L861Q mutant (Lee et al. 2006); EGFR D770_N771insNPG mutant (Greulich et al. 2005, Xu et al. 2007); EGFR N771_H773dup mutant (Xu et al. 2007); EGFR K739_I744dup mutant (Xu et al. 2007); EGFR A767_V769dup mutant (Xu et al. 2007); EGFR E746_A750del;T790M double mutant (Shimamura et al. 2005).
Reaction - small molecule participants:
PI(3,4,5)P3 [plasma membrane]
ADP [cytosol]
ATP [cytosol]
PI(4,5)P2 [plasma membrane]
Reactome.org reaction link: R-HSA-1226014
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Reaction input - small molecules:
ATP(4-)
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate(5-)
Reaction output - small molecules:
1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate(7-)
ADP(3-)
Reactome.org link: R-HSA-1226014