The Akt Pathway (or PKB pathway), also known as PI3K-Akt Pathway, is a signal transduction pathway that promotes survival and growth in response to extracellular signals. The Akt Pathway is a major focus of attention because of its critical role in regulating diverse cellular functions including metabolism, growth, proliferation, survival, transcription and protein synthesis. Key proteins involved are phosphatidylinositol 3-kinase (PI3K) and Akt, or Protein Kinase B.
The Akt signaling cascade is activated by receptor tyrosine kinases, integrins, B and T cell receptors, cytokine receptors, G-protein-coupled receptors and other stimuli that induce production of phospha- tidylinositol (3,4,5) trisphosphates (PIP3) by phosphoinositide 3-kinase (PI3K). Akt is dephosphorylated by protein phosphatase 2A (PP2A) and the PH-domain leucine-rich-repeat-containing protein phosphatases (PHLPP1/2). In addition, the tumor suppres- sor phosphatase and tensin homolog (PTEN) inhibits Akt activity by dephosphorylating PIP3. There are three highly related isoforms of Akt (Akt1, Akt2 and Akt3), Akt regulates cell growth through its effects on the TSC1/TSC2 complex and mTORC signaling. Akt contributes to cell proliferation via phosphorylation of the CDK inhibitors p21 and p27. Akt also regulates NF-κB signaling by phosphorylating IKKα and Tpl2. Due to the critical role of Akt/PKB in regulating diverse cellular functions it is an important therapeutic target for the treatment of human disease.