PI3K/AKT/mTOR pathway

Overview

The PI3K/AKT/mTOR pathway is a critical signaling pathway that regulates various cellular processes, including growth, proliferation, survival, and metabolism. This pathway is frequently activated in cancer and is a target for therapeutic intervention.

Diagram of the PI3K/AKT/mTOR pathway.

Components of the Pathway

Phosphoinositide 3-kinases (PI3K)

Phosphoinositide 3-kinases (PI3K) are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, and survival. PI3K is activated by various growth factors and hormones, leading to the production of phosphatidylinositol (3,4,5)-trisphosphate (PIP3).

AKT

AKT (also known as protein kinase B) is a serine/threonine-specific protein kinase that plays a key role in multiple cellular processes. Once activated by PIP3, AKT phosphorylates a range of downstream targets involved in cell survival and metabolism.

Mammalian Target of Rapamycin (mTOR)

The mammalian target of rapamycin (mTOR) is a central regulator of cell metabolism, growth, proliferation, and survival. mTOR forms two distinct complexes: mTORC1 and mTORC2, each with unique roles in the cell.

Pathway Activation

The PI3K/AKT/mTOR pathway is activated by various extracellular signals, including growth factors like insulin and insulin-like growth factor 1 (IGF-1). Upon activation, PI3K converts PIP2 to PIP3, which recruits AKT to the plasma membrane where it is phosphorylated and activated. Activated AKT then phosphorylates and regulates a variety of downstream targets, including mTOR.

Role in Cancer

The PI3K/AKT/mTOR pathway is often dysregulated in cancer, leading to increased cell growth and survival. Mutations in genes encoding components of this pathway, such as PIK3CA, PTEN, and AKT1, are common in various cancers. Targeting this pathway with specific inhibitors is a major focus of cancer therapy research.

Therapeutic Targeting

Inhibitors of the PI3K/AKT/mTOR pathway are being developed and tested in clinical trials for their potential to treat cancer. These include PI3K inhibitors, AKT inhibitors, and mTOR inhibitors such as rapamycin and its analogs (rapalogs).

Related Pages

• Signal transduction
• Cell cycle
• Apoptosis
• Cancer