PI3K/Akt/mTOR
The phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) signaling pathways are two pathways that is important to many aspects of cell growth and survival, in physiological as well as in pathological conditions (e.g., cancer. PI3Ks constitute a lipid kinase family. Class I PI3Ks are heterodimers composed of a catalytic subunit and an adaptor called p85. It is activated by receptors with protein tyrosine kinase activity. Akt kinases belong to the AGC kinase family. mTOR is an important protein for life. When ligand binds, phosphorylated tyrosine residing in activated RTKs will bind to p85. After binding with p85, it releases p110 subunit. Activated p110 phosphorylated the PIP2 into the second messenger PIP3. This step can be reversed by the PI3K antagonist PTEN. PIP3 will recruit the downstream Akt to inside membranes and phosphorylates Akt on its serine/threonine kinase sites (Thr308 and Ser473). Activated Akt is involved in the downstream mTORC1 mediated response to biogenesis of protein and ribosome. There are several genes that belong to the PI3K/Akt pathway have been implicated in the pathophysiology of solid tumors and sensitivity/resistance to chemotherapy. The researchers target is to study the PI3K/AKt/mTOR signalling and make therapeutics drugs for Cancer.
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