Erschienen in:
01.12.2011 | Oral presentation
The phosphatidylinositol-3 kinase/mTOR pathway: new agents
verfasst von:
CL Arteaga
Erschienen in:
Breast Cancer Research
|
Sonderheft 2/2011
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Excerpt
The phosphatidylinositol-3 kinase (PI3K) pathway is overall the most frequently mutated pathway in cancer, with mutation and/or amplification of the genes encoding the PI3K catalytic subunits p110α (PIK3CA) and p110β (PIK3CB), the PI3K regulatory subunit p85α (PIK3R1), receptor tyrosine kinases (RTKs) such as HER2 (ERBB2) and FGFR1, the PI3K activator K-Ras, the PI3K effectors AKT1, AKT2, and PDK1, and loss of the lipid phosphatases PTEN and INPP4B. PI3K is activated by growth factor RTKs and G-protein-coupled receptors (GPCRs). PI3K activates Akt, which, in turn, phosphorylates and inactivates Tuberin (TSC2), a GTPase-activating protein of the Ras homologue Rheb. Inactivation of Tuberin allows GTP-bound Rheb to accumulate and activate the mTOR/Raptor (TORC1) complex, which regulates protein synthesis and cell growth. mTOR also couples with Rictor to form the TORC2 complex, which phosphorylates and activates AKT. …