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PI3 K/Akt/mTOR Signaling
The PI3K/AKT/mTOR pathway is an intracellular signaling pathway important in apoptosis and hence cancer (e.g.breast cancer and glioblastoma). The phosphatidylinositol 3-kinases (PI3Ks) are a family of lipid kinases whose primary biochemical function is to phosphorylate the 3-hydroxyl group of phosphoinositides PI3K activation activates AKT. AMP-activated protein kinase (AMPK) was initially identified as a serine/threonine kinase that negatively regulates several key enzymes of the lipid anabolism. AMPK is regarded as the major energy-sensing kinase that activates a whole variety of catabolic processes in multicellular organisms such as glucose uptake and metabolism, while simultaneously inhibiting several anabolic pathways, such as lipid, protein, carbohydrate biosynthesis and mTOR.
The proline-rich Akt substrate of 40 kDa (PRAS40) acts at the intersection of the Akt- and mammalian target of rapamycin (mTOR)-mediated signaling pathways. The protein kinase mTOR is the catalytic subunit of two distinct signaling complexes, mTOR complex 1 (mTORC1) and mTORC2, that link energy and nutrients to the regulation of cellular growth and energy metabolism. Alterations in Akt and mTOR activity have been linked to the progression of multiple diseases such as cancer and type 2 diabetes.