AKT Signaling Pathway

AKT Signaling Pathway Background

The Akt Pathway, or PI3K-Akt Pathway is involved in fundamental cellular processes including protein synthesis, proliferation and survival. AKT also plays a regulatory role in angiogenesis and metabolism. The AKT pathway is activated by factors that induce PI3K which in turn activates mTOR pathways. The AKT signaling pathway plays an important regulatory role in many cellular survival pathways, primarily as an inhibitor of apoptosis. AKT signaling has been implicated in various cancers and is an active area of interest for anti-cancer therapeutics. The pathway can be activated by a range of signals, including hormones, growth factors and components of the extracellular matrix (ECM). PI3K can also be activated by G protein-coupled receptors (GPCR). Akt binds PIP3 through its pleckstrin homology (PH) domain, resulting in translocation of Akt to the membrane. PDK1, which is also brought to the membrane through its PH domain, phosphorylates Akt within its activation loop at Thr308. A second phosphorylation at Ser473 within the carboxy terminus is also required for activity and is carried out by the mTOR-rictor complex, mTORC2. AKT is activated by PI3K, which itself is activated by several upstream signaling pathways such as insulin receptors, receptor tyrosine kinases, G protein coupled receptors, cytokine receptors, etc. After activation, it targets several downstream molecules and change their activity by phosphorylation or complex formation. AKT is involved in cell proliferation, glucose metabolism, cell survival, cell cycle, protein synthesis, and in neuronal morphology and plasticity by regulation of several downstream molecules shown in this figure. AKT is involved in cell proliferation through interaction with a number of proteins involved in cell cycle Akt is also a key player in cardiovascular disease through its role in cardiac growth, angiogenesis, and hypertrophy. The pathway is highly regulated by multiple mechanisms, often involving cross-talk with other signalling pathways.

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