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PI3K-Akt-mTOR Pathway


Akt, also known as protein kinase B (PKB) is a serine/threonine kinase that plays an important role in oncogenesis and the cellular processes of metabolism, apoptosis and autophagy. AKT is activated through phosphorylation (at either T308 or S473) by an activating kinase after being recruited to the plasma membrane by PIP3. The availability of PIP3 at the plasma membrane is tightly regulated by the opposing processes of PI 3-Kinase (PI3K), which phosphorylates PIP2 to PIP3, and PTEN, which dephosphorylates PIP3 and abrogates AKT recruitment. Constitutive activation of PI3K or loss of PTEN function are both associated with oncogenic progression.


The mammalian target of rapamycin (mTOR) has been identified as the critical downstream mediator of AKT’s oncogenic properties. Together with the proteins GbL, Raptor and PRAS40, mTOR forms the mTORC1 complex. This complex induces cell growth by stimulating protein synthesis, driving cell cycle progression and inhibiting autophagy. mTOR can also associate with different proteins to form a functionally distinct complex, the rapamycin-insensitive mTORC2. It has recently been discovered that mTORC2 directly phosphorylates and activates AKT, indicating that mTOR has a complicated role both upstream and downstream of AKT. GeneTex is proud to offer a complete line of antibodies for studying the various components of the PI3K-Akt-mTOR signaling pathway.