Detail for PI3K/AKT/mTOR signaling pathway


Full Name

Phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway

Gene Name

Unknown

Related Disease

  • Liver cancer [ref.1]

Therapy Method

Function

PIK3CD (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Delta) is a Protein Coding gene. Diseases associated with PIK3CD include Immunodeficiency 14 and Hepatosplenic T-Cell Lymphoma. Among its related pathways are mTOR Pathway and Focal Adhesion. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and kinase activity. An important paralog of this gene is PIK3CB.AKT1 (AKT Serine/Threonine Kinase 1) is a Protein Coding gene. Diseases associated with AKT1 include Cowden Syndrome 6 and Proteus Syndrome. Among its related pathways are ERK Signaling and mTOR Pathway. Gene Ontology (GO) annotations related to this gene include identical protein binding and protein kinase activity. An important paralog of this gene is AKT3.

The PI3K/AKT/mTOR pathway is an intracellular signaling pathway important in regulating the cell cycle. Therefore, it is directly related to cellular quiescence, proliferation, cancer, and longevity. PI3K activation phosphorylates and activates AKT, localizing it in the plasma membrane. AKT can have a number of downstream effects such as activating CREB, inhibiting p27, localizing FOXO in the cytoplasm, activating PtdIns-3ps, and activating mTOR which can affect transcription of p70 or 4EBP1. There are many known factors that enhance the PI3K/AKT pathway including EGF, shh, IGF-1, insulin, and CaM. Both leptin and insulin recruit PI3K signalling for metabolic regulation. The pathway is antagonized by various factors including PTEN, GSK3B, and HB9. In many cancers, this pathway is overactive, thus reducing apoptosis and allowing proliferation. This pathway is necessary to promote growth and proliferation over differentiation of adult stem cells, neural stem cells specifically.

Reference

  • [1] Curcumin inhibits the growth of liver-cancer stem cells through the phosphatidylinositol 3-kinase/protein kinase B/mammalian-target-of rapamycin signaling pathway.
    Exp Ther Med.2018 Apr;15(4):3650-3658. [ 29545895 ]

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