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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• Baumann, C. A. et al. (2000) CAP defines a second signalling pathway required for insulin-stimulated glucose transport. Nature 407, 202-207. Applications: Western Blot
• 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
• 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
• Okkenhaug, K. et al. (2002) Impaired B and T cell antigen receptor signaling in p110delta PI 3-kinase mutant mice. Science 297 (5583), 1031-1034. Applications: Western Blotting
• Wettey, F. R. et al. (2002) Controlled Elimination of Clathrin Heavy-Chain Expression in DT40 Lymphocytes. Science 297, 1521-1525. Applications: Western Blotting
• Sutherland, C. L. et al. (2002) UL16-Binding Proteins, Novel MHC Class I-Related Proteins, Bind to NKG2D and Activate Multiple Signaling Pathways in Primary NK Cells. J. Immunol. 168, 671-679. Applications: Western Blotting
• Holland, E. C. et al. (2000) Combined activation of Ras and Akt in neural progenitors induces glioblastoma formation in mice. Nat. Genet. 25, 55-57. Applications: Western Blot
• Shan, X. et al. (2000) Deficiency of PTEN in Jurkat T cells causes constitutive localization of Itk to the plasma membrane and hyperresponsiveness to CD3 stimulation. Mol. Cell. Biol. 20, 6945-6957. Applications: Western Blot
• Sibilia, M. et al. (2000) The EGF receptor provides an essential survival signal for SOS-dependent skin tumor development. Cell 102, 211-220. Applications: Western Blot
• Tilton, B. et al. (2000) Signal transduction by CXC chemokine receptor 4: stromal cell-derived factor 1 stimulates prolonged protein kinase b and extracellular signal-regulated kinase 2 activation in T lymphocytes. J. Exp. Med. 192, 313-324. Applications: Western Blot
• Guo, A. et al. (2008) Proc Natl Acad Sci U S A 105, 692-7. Applications: Western Blotting
• Fukuhara, S. et al. (2008) Nat Cell Biol 10, 513-26. Applications: Western Blotting
• Fujita, H. et al. (2005) Biochem Pharmacol 69, 1773-84. Applications: Western Blotting
• Engelman, J.A. et al. (2008) Nat Med Applications: Western Blotting
• Hoshino, Y. et al. (2004) Mol Reprod Dev 69, 77-86. Applications: IF-IC (In Cells)
• Chung, Y.W. et al. (2011) J Biol Chem 286, 29681-90. Applications: Western Blotting
• Fonseca, B.D. et al. (2011) J Biol Chem 286, 27111-22. Applications: Western Blotting
• Inoue, T. (2008) J Leukoc Biol 83, 1218-29. Applications: Western Blotting
• Sakaguchi, M. et al. (2008) Mol Biol Cell 19, 78-85. Applications: Western Blotting
• Kawase, T. et al. (2009) Cell 136, 535-50. Applications: Western Blotting
• Yamada, O. et al. (2008) J Leukoc Biol 83, 1240-8. Applications: Western Blotting
• Ohtani, M. et al. (2008) Blood 112, 635-43. Applications: Western Blotting
• Ohne, Y. et al. (2008) J Biol Chem 283, 31861-70. 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
• Hoshino, Y. et al. (2007) Dev Biol 314, 215-23. Applications: IF-IC
• Kitamura, T. et al. (2008) Nat Cell Biol 10, 329-37. Applications: Western Blotting
• Nishimura, M. et al. (2009) Mol Cell Biol 29, 5529-39. 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
• Sakaue, H. et al. (2003) J Biol Chem. 278, 38870-4. Applications: Western Blotting
• Nishioka, Y. et al.(2008) Blood 111, 5086-92. Applications: Flow

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Phospho-Akt (Ser473) Antibody

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