PI3K-AKT-mTOR信号通路.docx

The PI3K/Akt/mTOR pathway plays an important role in apoptosis. Activated PI3K generates phosphatidylinositol-3,4,5-triphosphate, which recruits PDK1 and Akt serine/threonine kinase at the plasma membrane. This results in activation of Akt. ?Akt activates multiple downstream targets, including the mTOR pathway. Akt in this patyway is flanked by two tumor suppressors, PTEN and TSC1/TSC2 heterodimer.Various /pharmacological_receptor-tyrosine-kinase.htmlreceptor tyrosine kinases (/pharmacological_receptor-tyrosine-kinase.htmlRTKs), such as /HER2.htmlhuman epidermal growth factor receptor 2 (/HER2.htmlHER2), /EGFR(HER).htmlepidermal growth factor receptor (/EGFR(HER).htmlEGFR), /IGF-1R.htmlinsulin-like growth factor receptor and /VEGFR-PDGFR.htmlvascular endothelial growth factor receptor, activate the growth and survive of cells in the manner of mobilizing the intracellular PI3K signaling pathway [12; 36]. The carcinogenic role of the PI3K pathway firstly came into the notice since mutation-induced abnormal cellular signaling was associated with malignant proliferation and growth [58]. Increasing evidence indicated that PI3K signaling pathway was usually found to be disordered in many kinds of cancers.THE PI3K FAMILY MEMBERSAll PI3K family members have the ability to phosphorylate the 3-hydroxyl group of phosphoinositides [9]. They could be generally classified into three classes according to their primary structure, regulation, and in vitro lipid substrate specificity [34]. Class I PI3Ks are heterodimers containing a regulatory subunit and a catalytic subunit, which might be involved in malignant transformation in many different cancer types. The genes of PIK3R1, PIK3R2 and PIK3R3 encode the regulatory subunit, namely p85 (α, ? and γ) [38]. p110 is the catalytic subunit of class IA PI3K. The function of PI3K enzymes is mainly depended on it. There are four isoforms of p110: α, ?, γ and δ, which are encoded by the genes of PIK3CA, PIK3CB, PI3KCG and PIK3CD, respectivel