Pathway information and image are provided courtesy of R&D Systems, a Bio-Techne Brand. Much more in-depth information about this pathway is available on their website Read more

Serine/threonine kinase Akt plays critical role in regulating diverse cellular functions including metabolism, growth, proliferation, survival, transcription and protein synthesis. There are three highly related isoforms of Akt (Akt1, Akt2 and Akt3), which share many substrates but isoform-specific Akt substrates have also been identified.

In cells, receptor tyrosin kinasese, integrins, B and T cell receptors, cytokine receptors, G-protein-coupled receptors and other stimuli induce phosphoinositide 3-kinase (PI3K) to produce phospha- tidylinositol (3,4,5) trisphosphates (PIP3) through activate factors such as Focal Adhesion Kinase (FAK), Integrin-Linked Kinase (ILK), B-Cell Receptor (BCR), Spleen Tyrosine Kinase (SKY) and Janus Kinase-1 (JAK1). PIP3 then harbors pleckstrin-homol- ogy (PH) domains of Akt. Akt is activated by Phosphoinositide-Dependent Kinase-1 (PDK1), mTORC2, Cell Division Cycle-37 (CDC37), Heat Shock Protein-90KD (HSP90) through phosphorylation, whereas Akt is dephosphorylated by tumor suppressor phosphatase and tensin homolog (PTEN) and SH2-Containing Inositol Phosphatase (SHIP).

Akt regulates cell growth through its effects on the TSC1/TSC2 complex and mTORC signaling. Akt contributes to cell proliferation through phosphorylation of the CDK inhibitors p21 and p27. Akt is a major mediator of cell survival through direct inhibition of pro-apoptotic signals generated by transcription factors like FoxO or inhibition of pro-apoptotic proteins like Bad. Akt activates I-KappaB Kinase (IKK), which ultimately leads to NF-KappaB activation and cell survival. In the presence of survival factors, Akt1 phosphorylates FKHRL1 (FOXO3), leading to the association of FKHRL1 with 14-3-3 proteins and its retention in the cytoplasm. WNK Lysine deficient Protein Kinase-1 (WNK1) is a physiologically relevant target of Insulin signaling through PI3K and Akt and functions as a negative regulator of Insulin-stimulated mitogenesis. Akt phosphorylates Yes-Associated Protein-1 (YAP), a transcription factor, which causes nuclear export and cytoplasmic localization. Akt also phosphorylates Androgen Receptor (AR) which causes a decrease in AR activity on the p21 promoter and cell cycle progression.