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The phosphoinositide-3-kinase- (PI3K-) Akt pathway has been involved in many critical cellular functions, including protein synthesis, cell cycle progression, proliferation, apoptosis, autophagy, and drug resistance in response to growth factor (EGF, PDGF, NGF, and VEGF), hormone (prostaglandin, PGE2), and cytokine (IL-17, IL-6, and IL-2) stimulation [85–87]. The binding of growth factor to its receptors directly stimulates class 1A PI3Ks bound via their regulatory subunit or adapter molecules such as the insulin receptor substrate (IRS) proteins, which subsequently triggers the activation of PI3K. Afterwards, the activated PI3K catalyzes the synthesis of phosphatidylinositol 3,4,5-triphosphate (PIP3), from phosphatidylinositol 4,5-bisphosphate (PIP2) [88]. The membranal PIP3, a signaling molecule, recruits and activates proteins that contain the pleckstrin homology (PH) domain such as the phosphoinositide-dependent protein kinase (PDK) and protein kinase B (Akt) serine/threonine kinases and the activation of PDK and Akt successively promotes the activation and transcription of their target genes (GSK3, FOXO, BAD, mTOR1, and p53) [89–92].
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