PI3K/AKT/mTOR pathway

PI3K/AKT/mTOR pathway is a critical cell signaling pathway that regulates several cellular processes, including cell growth, proliferation, and survival. This pathway is often dysregulated in various diseases, particularly in cancer, making it a significant target for therapeutic intervention.

Overview

The PI3K/AKT/mTOR pathway is initiated by the binding of a growth factor to its receptor tyrosine kinase (RTK). This binding activates phosphatidylinositol 3-kinase (PI3K), which phosphorylates and activates AKT, a serine/threonine kinase. AKT then activates the mammalian target of rapamycin (mTOR), a key regulator of cell growth and proliferation.

Components

PI3K

PI3K is a lipid kinase that phosphorylates phosphatidylinositol 4,5-bisphosphate (PIP2) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 serves as a second messenger that recruits AKT to the plasma membrane.

AKT

AKT, also known as Protein Kinase B (PKB), is a serine/threonine kinase that is activated by PI3K. Once activated, AKT phosphorylates a variety of substrates involved in cell survival, growth, and proliferation.

mTOR

mTOR is a serine/threonine kinase that regulates cell growth, proliferation, and survival. It is the target of the immunosuppressive drug rapamycin.

Role in Disease

Dysregulation of the PI3K/AKT/mTOR pathway is often observed in various diseases, particularly in cancer. Mutations in PI3K, AKT, or mTOR can lead to constitutive activation of the pathway, promoting cell survival and proliferation and contributing to tumorigenesis.

Therapeutic Target

Given its critical role in cell growth and survival, the PI3K/AKT/mTOR pathway is a significant target for therapeutic intervention. Several inhibitors targeting different components of this pathway are currently in clinical trials for the treatment of various cancers.

See Also

• Signal transduction
• Cancer
• Phosphatidylinositol 3-kinase
• AKT
• mTOR