PI3K/AKT/mTOR pathway

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​The PI3K/AKT/mTOR pathway is an intracellular signaling pathway involved in numerous biological processes such as cell proliferation and apoptosis, angiogenesis, and glucose metabolism^1,2. The pathway is initiated by the binding of extracellular growth factors to transmembrane receptor tyrosine kinases (RTKs) such as EGFR^3,4, upon which phosphatidylinositol 3-kinase (PI3K) is activated and subsequently activates the serine/threonine protein kinase B (PKB/AKT). This leads to serine and/or threonine phosphorylation of a range of downstream substrates which often themselves are kinase/phosphatases or other signaling molecules which mediate the various cell biologies.

Dysregulation of this pathway has been associated with the development of a number of human diseases including, diabetes, autoimmunity, and cancer⁵. Enhanced activation can occur through several mechanisms, including inactivation of negative regulator phosphatase and tensin homolog (PTEN) and activating mutations, and gene amplification of the gene encoding PIK3CA⁶.

Agents that target the regulators in this pathway show attractive therapeutic potential, with multiple drugs targeting either single PI3K, AKT, or downstream effector mechanistic target of rapamycin (mTOR) or both PI3K and mTOR (dual inhibitors) already either commercialized or in development^2,3,7.

What to expect

• Discover the key targets involved in the PI3K/AKT/mTOR pathway and their corresponding interactions
• Find high-quality reagents including antibodies and cell lines to your target of choice

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References

1. Xie, Y, et al. PI3K/Akt signaling transduction pathway, erythropoiesis and glycolysis in hypoxia Molecular Medicine Reports. 19(2), 783-791 (2019).
2. Keppler-Noreuil, et al. Somatic Overgrowth Disorders of the PI3K/AKT/mTOR Pathway & Therapeutic Strategies Am J Med Genet C Semin Med Genet. 172(4),  402-421 (2017).
3. Xu, F., Na, L. et al. Roles of the PI3K/AKT/mTOR signaling pathways in neurodegenerative diseases and tumors Cell & Bioscience. 10 (2020).
4. Papadimitrakopoulou, V. Development of PI3K/AKT/mTOR Pathway Inhibitors and Their Application in Personalized Therapy for Non–Small-Cell Lung Cancer Journal of Thoracic Oncology. 7, p1315-1326 (2012).
5. West, K.A. et al. Activation of the PI3K/Akt pathway and chemotherapeutic resistance Drug Resistance Updates. 5, 234-248 (2002).
5. Paes, J.E., and Ringel, M.D. Dysregulation of the Phosphatidylinositol 3-kinase Pathway in Thyroid Neoplasia Endocrinol Metab Clin North Am. 37 (2008).
5. Haddadi, N. et al. PTEN/PTENP1: ‘Regulating the regulator of RTK-dependent PI3K/Akt signaling’, new targets for cancer therapy Molecular Cancer. 17 (2018).