Akt Kinase / PKB (Protein Kinase B)

Sino Biological provides a comprehensive set of tools for Akt/PKB related studies, including proteins, antibodies (rabbit mAbs, mouse mAbs, and rabbit pAbs), ELISA kits, and ORF cDNA clones. The serine/threonine kinase Akt/PKB is a central node in cell signaling downstream of growth factors, cytokines, and other cellular stimuli. Akt/PKB plays a key role in multiple cellular processes such as cell survival, growth, proliferation, angiogenesis, metabolism, and migration. In humans, there are three members in the Akt family: Akt1, Akt2, and Akt3.

Akt/PKB Products

• AKT1 
• AKT2
• AKT3

Akt/PKB Background

The serine/threonine protein kinase Akt/PKB is a central node in cell signaling downstream of growth factors, cytokines, and other cellular stimuli. Akt/PKB plays a key role in multiple cellular processes such as cell survival, growth, proliferation, angiogenesis, metabolism, and migration. The Akt/PKB family has three members: Akt1/PKBα, Akt2/PKBβ, and Akt3/PKBγ, which have extensive homology to protein kinases A, G, and C within their kinase domains and are, therefore, members of the AGC kinase family.

Akt/PKB enhances the survival of cells by blocking the function of proapoptotic proteins and processes. Akt negatively regulates the function or expression of several Bcl-2 homology domain 3 (BH3)-only proteins, which exert their proapoptotic effects by binding to and inactivating prosurvival Bcl-2 family members. In addition, under some conditions, the PI3K-Akt pathway activates NFκB survival signaling or inhibits JNK/p38 apoptotic signaling. Therefore, Akt also possibly exerts some of its cell-survival effects through crosstalk with other pathways or through effects on nutrient uptake and metabolism.

Akt/PKB promotes cell growth through activation of mTOR complex 1 (mTORC1), which is regulated by both nutrients and growth factor signaling. The mechanism by which Akt regulate mTORC1 signaling has not yet been determined. Akt has been suggested to directly phosphorylate mTOR on S2448, which often correlates with mTORC1 activation. Another possibility is through the intermediate tuberous sclerosis complex 2 (TSC2 or tuberin). It has been suggested that TSC2 is a critical negative regulator of mTORC1 signaling and that Akt-mediated phosphorylation inhibits TSC2 function.

Akt/PKB activation can also stimulate proliferation through multiple downstream targets impinging on cell-cycle regulation. Several groups have independently found that Akt phosphorylates the p27Kip1 cyclin-dependent kinase inhibitor on T157, and this leads to cytosolic sequestration via 14-3-3 binding. Akt has also been found to phosphorylate the cyclin-dependent kinase inhibitor p21Cip1/WAF1 on T145, and this phosphorylation leads to p21 cytosolic localization.

Akt2 is required for the insulin-induced translocation of glucose transporter 4 (GLUT4) to the plasma membrane. Glycogen synthase kinase 3 (GSK-3) could be inhibited upon phosphorylation by Akt, which results in promotion of glycogen synthesis.

Akt/PKB plays important roles in both physiological and pathological angiogenesis through effects in both endothelial cells and cells producing angiogenic signals, such as tumor cells. In endothelial cells, the PI3K-Akt pathway is robustly activated by vascular endothelial growth factor (VEGF), and phosphorylation of the Akt targets is likely to contribute to endothelial cell survival, growth, and proliferation. In addition, Akt activates endothelial nitric oxide synthase (eNOS) through direct phosphorylation of S1177. The release of NO produced by activated eNOS can stimulate vasodilation, vascular remodeling, and angiogenesis. Akt signaling also leads to an increased production of the hypoxia-inducible factor α (HIF1α and HIF2α) transcription factors, which leads to expression and subsequent secretion of VEGF and other angiogenic factors.

Akt/PKB Related Studies

1. Song G, et al. (2005) The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med. 9(1):59-71.
2. Yoeli-Lerner M, et al. (2006) Akt/PKB signaling in cancer: a function in cell motility and invasion. Cell Cycle. 5(6):603-5.
3. Shiojima I, et al. (2006) Regulation of cardiac growth and coronary angiogenesis by the Akt/PKB signaling pathway. Genes Dev. 20(24):3347-65.
4. Manning BD, et al. (2007) AKT/PKB signaling: navigating downstream. Cell. 129(7):1261-74.