Akt/PKB signaling pathway

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Akt/PKB Signaling Pathway

The Akt/PKB signaling pathway is a crucial intracellular signaling pathway in eukaryotic cells that is involved in regulating various cellular processes, including cell growth, proliferation, metabolism, survival, and angiogenesis. The pathway is named after the serine/threonine-specific protein kinase Akt, also known as Protein Kinase B (PKB).

Components of the Akt/PKB Signaling Pathway

Phosphoinositide 3-Kinase (PI3K)

Phosphoinositide 3-kinase (PI3K) is an enzyme that phosphorylates the 3' hydroxyl group of the inositol ring of phosphatidylinositol. PI3K is activated by various growth factors and hormones through receptor tyrosine kinases (RTKs) and G protein-coupled receptors (GPCRs).

Phosphatidylinositol (3,4,5)-trisphosphate (PIP3)

Upon activation, PI3K converts phosphatidylinositol (4,5)-bisphosphate (PIP2) into phosphatidylinositol (3,4,5)-trisphosphate (PIP3). PIP3 serves as a docking site for proteins with pleckstrin homology (PH) domains, including Akt.

Akt/PKB

Akt is a central kinase in the pathway and has three isoforms: Akt1, Akt2, and Akt3. Akt is recruited to the plasma membrane by binding to PIP3 through its PH domain. Once at the membrane, Akt is phosphorylated and activated by phosphoinositide-dependent kinase-1 (PDK1) and the mammalian target of rapamycin complex 2 (mTORC2).

Downstream Targets

Activated Akt phosphorylates a variety of downstream targets, including:

• Glycogen synthase kinase 3 (GSK-3)
• Forkhead box O (FOXO) transcription factors
• Bcl-2-associated death promoter (BAD)
• mTOR complex 1 (mTORC1)

Functions of the Akt/PKB Signaling Pathway

Cell Growth and Proliferation

Akt promotes cell growth and proliferation by activating mTORC1, which in turn stimulates protein synthesis and ribosome biogenesis.

Metabolism

Akt regulates glucose metabolism by promoting the translocation of glucose transporter type 4 (GLUT4) to the cell membrane and by inhibiting GSK-3, which enhances glycogen synthesis.

Cell Survival

Akt enhances cell survival by inhibiting pro-apoptotic factors such as BAD and by activating anti-apoptotic factors like Bcl-2.

Angiogenesis

Akt promotes angiogenesis by upregulating the expression of vascular endothelial growth factor (VEGF).

Clinical Significance

Dysregulation of the Akt/PKB signaling pathway is implicated in various diseases, including cancer, diabetes, and cardiovascular diseases. Overactivation of Akt is commonly observed in many types of cancer, making it a target for therapeutic intervention.

See Also

• Signal transduction
• Receptor tyrosine kinase
• G protein-coupled receptor
• mTOR signaling pathway
• Apoptosis