PI3K/AKT Pathway Analysis

Improved Essays
PTEN regulation of PI3K/AKT Pathway
In the first lecture of class we discussed a diagram from Saltiel and Kahn 2001. The diagram presented the phosphoinositide 3-kinase (PI3K) and Serine/Threonine Kinase (AKT)/ Protein Kinase B (PKB) pathway inhibition of the insulin receptor and insulin receptor substrate (IRS) through activation of mammalian target of rapamycin (mTOR) and a recent study reports similar findings (Mathew et al. 2016; Saltiel and Kahn 2001). Activation of PI3K/AKT signaling pathway can be triggered by transmembrane Receptor Tyrosine Kinase (RTK) signaling. When an extracellular growth factor binds to the RTK it dimerizes and triggers autophosphorylation through the homologous interaction of each monomer. The dimerized RTK is dependent on the
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Additionally, PI3K can bind to a GTP bound activated Ras protein. Activated PI3K migrates inside the cell to phosphatidylinositol 4,5-bisphosphate (PIP2), which is anchored in the cell membrane by two fatty acid tails. PI3K phosphorylates PIP2 on the 3rd carbon position of the inositol resulting in phosphatidylinositol 3,4,5-triphosphate (PIP3). PIP3 triggers the activation of AKT/PKB signal pathway. AKT is a protooncogene protein that inhibits programmed cell death through binding of BAX preventing it from degrading the mitochondrial membrane that result in caspase-induced apoptosis. Furthermore, activation of AKT pathway signals Rheb that triggers mTOR activation translation factor S6K, which binds to the large ribosome subunit and promotes RNA translation (Davis et al., 2014). This suggest that AKT activation enables cell proliferation by inducing increased protein translation and cell growth. The activated AKT pathway also promotes phosphorylation of the tumor suppressor FOXO that results in increased FOXO ubiquination and subsequently the degradation of FOXO via proteasomes (Ruscetti and Wu 2013). This suggests that AKT prevents FOXO from inhibiting cell

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