PI3KAKTmTORWeges

The PI3K/Akt/mTOR pathway is a crucial signaling cascade involved in numerous cellular processes including cell growth, proliferation, survival, and metabolism. This pathway is initiated by the activation of phosphatidylinositol 3-kinase (PI3K), which phosphorylates phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 3,4,5-trisphosphate (PIP3) at the plasma membrane. PIP3 then recruits downstream effectors such as the kinase Akt (also known as protein kinase B) and phosphoinositide-dependent kinase-1 (PDK1) to the membrane, leading to Akt phosphorylation and activation.

Activated Akt can then phosphorylate a wide range of substrates, influencing various cellular functions. One of its key targets is the mammalian target of rapamycin (mTOR), a serine/threonine kinase that exists in two distinct complexes: mTORC1 and mTORC2. Akt can indirectly activate mTORC1, which plays a central role in regulating protein synthesis, cell growth, and metabolism by controlling the activity of downstream targets like S6 kinase and 4E-BP1. mTORC2, on the other hand, is involved in cytoskeletal organization and cell survival, and is regulated by Akt in a feedback loop.

Dysregulation of the PI3K/Akt/mTOR pathway is implicated in a variety of diseases, most notably cancer, where aberrant activation can promote tumor growth, survival, and metastasis. It also plays a role in metabolic disorders such as diabetes and obesity, as well as neurological conditions and immune responses. Consequently, this pathway is a major target for therapeutic interventions, with several drugs aimed at inhibiting specific components being developed and utilized for cancer treatment.