PI3K / Akt Signaling

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Akt, also referred to as PKB or Rac, plays a critical role in controlling survival and apoptosis (1-3). This protein kinase is activated by insulin and various growth and survival factors to function in a wortmannin-sensitive pathway involving PI3 kinase (2,3). Akt is activated by phospholipid binding and activation loop phosphorylation at Thr308 by PDK1 (4) and by phosphorylation within the carboxy terminus at Ser473. The previously elusive PDK2 responsible for phosphorylation of Akt at Ser473 has been identified as mammalian target of rapamycin (mTOR) in a rapamycin-insensitive complex with rictor and Sin1 (5,6). Akt promotes cell survival by inhibiting apoptosis through phosphorylation and inactivation of several targets, including Bad (7), forkhead transcription factors (8), c-Raf (9), and caspase-9. PTEN phosphatase is a major negative regulator of the PI3 kinase/Akt signaling pathway (10). LY294002 is a specific PI3 kinase inhibitor (11). Another essential Akt function is the regulation of glycogen synthesis through phosphorylation and inactivation of GSK-3α and β (12,13). Akt may also play a role in insulin stimulation of glucose transport (12). In addition to its role in survival and glycogen synthesis, Akt is involved in cell cycle regulation by preventing GSK-3β-mediated phosphorylation and degradation of cyclin D1 (14) and by negatively regulating the cyclin dependent kinase inhibitors p27 Kip (15) and p21 Waf1/CIP1 (16). Akt also plays a critical role in cell growth by directly phosphorylating mTOR in a rapamycin-sensitive complex containing raptor (17). More importantly, Akt phosphorylates and inactivates tuberin (TSC2), an inhibitor of mTOR within the mTOR-raptor complex (18,19).

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11. Vlahos, C.J. et al. (1994) J Biol Chem 269, 5241-8.
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18. Inoki, K. et al. (2002) Nat Cell Biol 4, 648-57.
19. Manning, B.D. et al. (2002) Mol Cell 10, 151-62.

• Asselin, E. et al. (2001) XIAP regulates Akt activity and caspase-3-dependent cleavage during cisplatin-induced apoptosis in human ovarian epithelial cancer cells. Cancer Res. 61, 1862-1868. Applications: Western Blot
• Bommakanti, R. K. et al. (2000) Dual regulation of Akt/protein kinase B by heterotrimeric G protein subunits. J. Biol. Chem. 275, 38870-38876. Applications: Western Blot
• Campbell, R. A. et al. (2001) Phosphatidylinositol 3-kinase/Akt-mediated activation of estrogen receptor alpha: a new model for anti-estrogen resistance. J. Biol. Chem. 276, 9817-9824. Applications: Western Blot
• Otero, D. C. et al. (2000) CD19-dependent activation of Akt kinase in B lymphocytes. J. Biol. Chem. 276, 1474-1478. Applications: Western Blotting
• Fukuda, T. et al. (2003) PINCH-1 is an obligate partner of integrin-linked kinase (ILK) functioning in cell shape modulation, motility, and survival. J. Biol. Chem. 278, 51324-51333. Applications: Western Blotting
• Patrucco, E. et al. (2004) PI3Kgamma modulates the cardiac response to chronic pressure overload by distinct kinase-dependent and -independent effects. Cell 118, 375-387. Applications: Western Blotting
• Huang, H. et al. (2001) PTEN Induces Chemosensitivity in PTEN-mutated Prostate Cancer Cells by Suppression of Bcl-2 Expression. J. Biol. Chem. 276, 38830-38836. Applications: Western Blotting
• Meng, F. et al. (2002) Akt Is a Downstream Target of NF-kappaB. J. Biol. Chem. 277, 29674-29680. Applications: Western Blotting
• Zubiaur, M. et al. (2002) CD38 Is Associated with Lipid Rafts and upon Receptor Stimulation Leads to Akt/Protein Kinase B and Erk Activation in the Absence of the CD3-zeta Immune Receptor Tyrosine-based Activation Motifs. J. Biol. Chem. 277, 13-22. Applications: Western Blotting
• Radisavljevic, Z. et al. (2000) Vascular endothelial growth factor up-regulates ICAM-1 expression via the phosphatidylinositol 3 OH-kinase/AKT/nitric oxide pathway and modulates migration of brain microvascular endothelial cells. J. Biol. Chem. 275, 20770-20774. Applications: Western Blot
• Rohani, M.G. et al. (2010) BMC Immunol 11, 53. Applications: Western Blotting
• Chung, Y.W. et al. (2011) J Biol Chem 286, 29681-90. Applications: Western Blotting
• Sykes, S.M. et al. (2011) Cell 146, 697-708. Applications: Western Blotting
• Sakaguchi, M. et al. (2008) Mol Biol Cell 19, 78-85. Applications: Western Blotting
• Yamada, O. et al. (2008) J Leukoc Biol 83, 1240-8. Applications: Western Blotting
• Nakasaki, M. et al. (2008) Bone 43, 869-79. Applications: Western Blotting
• Oneyama, C. (2008) Mol Cell 30, 426-36. Applications: Western Blotting
• Kitamura, T. et al. (2008) Nat Cell Biol 10, 329-37. Applications: Western Blotting
• Nemoto, S. et al. (2009) J Biol Chem 284, 10422-32. Applications: Western Blotting
• Kato, T. et al. (2008) Diabetes 57, 2382-92. Applications: Western Blotting
• Nishioka, Y. et al.(2008) Blood 111, 5086-92. Applications: Flow

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Akt Antibody

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