The phosphatidylinositol 3' –kinase (PI3K)-Akt signaling pathway is an intracellular signaling pathway important in regulating the cell cycle and is activated by many types of cellular stimuli or toxic insults.
It regulates fundamental cellular functions such as transcription, translation, proliferation, growth, and survival in response to extracellular signals. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates.
As shown in following picture, activation of growth factor receptor protein tyrosine kinases including epidermal growth factor receptor (EGFR) by external growth factors results in auto-phosphorylation on tyrosine residues and subsequent events to activate these intracellular pathways.
PI3K is recruited to the membrane by directly binding to phosphotyrosine consensus residues of growth factor receptors or adaptors through one or both SH2 domains in the adaptor subunit. This leads to allosteric activation of the catalytic subunit. Activation results in production of the second messenger phosphatidylinositol-3, 4, 5-trisphosphate (PIP3).
The lipid product of PI3K, PIP3, recruits a subset of signaling proteins with pleckstrin homology (PH) domains to the membrane, including PDK1 and Akt. PTEN, is a PI-3, 4, 5-P3 phosphatase, which negatively regulates the PI3K/Akt pathway.
Once activated, Akt mediates the activation and inhibition of several targets, resulting in cellular survival, growth and proliferation through various mechanisms.
In the mechanism of PI3K-Akt signaling pathway, the key molecules involved in this signaling pathway are receptor tyrosine kinase (RTKs), phosphatidylinositol 3-kinase (PI3K), phosphatidylinositol-4,5-bisphosphate (PIP2), phosphatidylinositol-3,4,5-bisphosphate (PIP3) and AKT/protein kinase B. You can click the link below to view more introduction of the two critical molecules https://www.cusabio.com/c-20715.html.
This article was written by a sweet guy from CUSABIO named PI3K-Akt Signaling Pathway and Cancer, including its history, mechanism and related diseases.
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