Page 33 - Cell biology PDC 2024

PIP3 recruits phosphoinositide dependent protein kinase 1 (PDK1) and
AKT to the plasma membrane. Their localization to the plasma
membrane close to each other promotes the phosphorylation and
activation of AKT
Activated Akt phosphorylates many proteins leading finally to inhibition
of apoptosis and promoting cell
Regulation of PI3K/AKT pathway:
PTEN (Phosphatase and tensin homolog on chromosome 10) is a tumor
suppressor gene that inhibit cell growth, proliferation, survival, protein
synthesis and transcription by inhibiting PI3K/AKT signaling pathway
It dephosphorylates the second messenger PI 3, 4, 5-triphosphate
(PIP3), thereby opposing the PI3K action and blocking therefore the
activation of downstream signaling events, including PDK and akt
The inactivation or dysfunction of PTEN results therefore in increased
PIP3 and persistent activation of PI3K effectors, excessive cell
proliferation and apoptosis resistance leading to many malignancies
such as: glioblastoma, hematological malignancies and leukemias

Figure 16: PI3K/AKT pathway

۳۲