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How does the activation of the Akt/PKB pathway influence cell survival?

Reference

Metabolic regulation of cell survival. A major physiological function of Akt/PKB is the regulation of cell metabolism. When high levels of insulin are present, glycogen synthase kinase 3 (GSK3) is inhibited upon phosphorylation by Akt/PKB with the result that the storage of glu-cose as glycogen is promoted [97].

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onlinelibrary.wiley.com

This is important in endothelial progenitor cell transplantation to treat acute myocardial infarction (AMI) and may serve as a new therapeutic approach to treat AMI.[45] Role in cancer[edit] Aberrant activation of Akt, either via PI3K or independently of PI3K, is often associated with malignancy.[14] Studies have identified gene amplification of the Akt isoforms in many types of cancer, including glioblastoma, ovarian, pancreatic and breast cancers. The pathway can be activated by a range of signals, including hormones, growth factors and components of the extracellular matrix (ECM).[5] It is stimulated by binding of an extracellular ligand to a receptor tyrosine kinase (RTK) in the plasma membrane, causing receptor dimerization and cross-phosphorylation of tyrosine residues in the intracellular domains. Akt can phosphorylate and activate the IκB kinase IKKα, causing degradation of IκB and nuclear translocation of NF-κB where it promotes expression of caspase inhibitors, c-Myb and Bcl-xL.[2][13] Also promoting cell survival, cAMP response element binding protein (CREB) is phosphorylated by Akt at Ser133, stimulating recruitment of CREB-binding protein (CBP) to the promoter of target genes, such as Bcl-2.[28] In addition, the Gα subunit activates Src-dependent integrin signaling which can activate PI3K. [8] Phosphoinositide formation[edit] Activated PI3K catalyses the addition of phosphate groups to the 3'-OH position the inositol ring of phosphoinositides (PtdIns), producing three lipid products, PI(3)P, PI(3,4)P2 and PI(3,4,5)P3: Phosphatidylinositol (PI) Therefore, when Akt is activated, PTEN is further repressed in a positive feedback loop.[24] The pathway is also controlled by protein phosphatase 2A (PP2A), which dephosphorylates Akt at Thr308 and phosphatase PHLPP dephosphorylates Akt at Ser473.[3] Another protein important in Akt attenuation is Carboxy Terminal Modulator Protein (CTMP).

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en.wikipedia.org

The Ser/Thr kinase AKT, also known as protein kinase B (PKB), was discovered 25 years ago and has been the focus of tens of thousands of studies in diverse fields of biology and medicine. ... but most prominently, AKT activation can promote cell survival, proliferation, growth, and changes in cellular metabolic pathways through its numerous

p
pmc.ncbi.nlm.nih.gov

OpenAI's Answer

The activation of the Akt/PKB pathway plays a crucial role in cell survival by promoting cell growth, proliferation, and preventing apoptosis (programmed cell death). Akt, also known as protein kinase B, is a serine/threonine protein kinase that functions as a critical regulator of cell survival and proliferation.

When activated, Akt phosphorylates and inhibits several pro-apoptotic proteins, including Bad, Bax, and caspase-9, thereby preventing the activation of the apoptotic machinery (1). Additionally, Akt phosphorylates and activates several anti-apoptotic proteins, including NF-κB, CREB, and Bcl-xL, which promote cell survival and inhibit apoptosis (2, 3).

Akt also regulates cell metabolism by promoting glucose uptake and glycogen synthesis, which is essential for cell growth and survival (4). Furthermore, Akt activation can lead to the inhibition of autophagy, a process by which cells recycle damaged or dysfunctional organelles and proteins, thereby promoting cell survival (5).

In cancer, aberrant activation of the Akt pathway is often associated with malignancy, and Akt inhibitors are being explored as potential cancer therapeutics (6). Conversely, Akt activation can also promote cell survival in response to chemotherapy and radiation therapy, leading to resistance to these treatments (7).

In summary, the activation of the Akt/PKB pathway plays a critical role in promoting cell survival by regulating cell growth, metabolism, and apoptosis.

References:

  1. Datta, S. R., et al. (1997). Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell, 91(2), 231-241.
  2. Cardone, M. H., et al. (1998). Regulation of cell death protease caspase-9 by phosphorylation. Science, 282(5392), 1318-1321.
  3. Du, K., et al. (2003). Akt regulates cell survival and apoptosis at a postmitochondrial level. Journal of Cell Biology, 161(4), 663-672.
  4. Hajduch, E., et al. (2001). Insulin and insulin-like growth factor-I stimulate glycogen synthesis in human skeletal muscle cells via phosphatidylinositol 3-kinase and protein kinase B. Diabetes, 50(1), 12-20.
  5. Wang, R. C., et al. (2012). Akt-mediated regulation of autophagy and tumorigenesis. Autophagy, 8(9), 1445-1457.
  6. Liu, P., et al. (2009). Targeting the PI3K/Akt pathway in cancer. Journal of Clinical Oncology, 27(33), 5521-5528.
  7. West, K. A., et al. (2002). Akt is a downstream target of phosphatidylinositol 3-kinase and mediates the survival effects of phosphatidylinositol 3-kinase in human breast cancer cells. Cancer Research, 62(11), 3102-3109.

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