Reaction: PI3K synthesizes PIP3 downstream of ALK mutants
- in pathway: Signaling by ALK fusions and activated point mutants
PI3K phosphorylates PIP2 to PIP3 downstream of activated ALK fusions and mutants, leading to activation of the AKT pathway as assessed by S473 phosphorylation (Bai et al, 2000; Slupianek et al, 2001; Slupianek et al, 2004; Chen et al, 2008). AKT signaling contributes to apoptotic escape and cellular proliferation through regulation of proteins such as CDKN1B/p27, CCND2 and BCL2L11/BIM, among others (Gu et al, 2004; Rassidakis et al, 2005; Marzec et al, 2007; reviewed in Chiarle et al, 2008; Hallberg and Palmer, 2013).
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-9712084
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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-9712084