Phospho-Akt (Ser473) (D9E) XP(

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Specificity / Sensitivity

Phospho-Akt (Ser473) (D9E) XP^® Rabbit mAb 能够检测内源性的丝氨酸(473位点)磷酸化的AKT蛋白。

Source / Purification

该单克隆抗体是采用合成的与人源AKT蛋白丝氨酸(473位)周围序列相对应的磷酸肽段免疫动物而生产的。Background

Akt,又被称为PKB 或 Rac，在细胞的生长和凋亡中起到关键作用(1-3)。被胰岛素（insulin）或各种生长及存活因子激活后，这个激酶在包括PI3K在内的对wortmannin敏感的通路中起作用(2,3)。磷脂结合可以调控Akt的激活，其苏氨酸308位点被PDK1环磷酸化(4)，并且在该蛋白碳链末端丝氨酸（473）位点磷酸化。以前研究认为PDK2在丝氨酸473位点磷酸化Akt，实际为哺乳类动物雷帕霉素靶蛋白（mTOR，mammalian target of rapamycin），其存在于包含rictor 和Sin1 的雷帕霉素非敏感复合体中。Akt促进细胞的生长通过抑制细胞的凋亡 ，例如Akt可以抑制下游靶蛋白Bad (7), forkhead 转录因子 (8), c-Raf (9), and caspase-9。PTEN 磷酸酶是抑制PI3 激酶/Akt信号通路的主要蛋白(10)。 LY294002是特异的 PI3 激酶的抑制剂(11)。Akt 的另外一个主要功能是通过磷酸化和抑制GSK-3α 和 β调控糖原的合成(12,13)。Akt 也可以调控insulin诱导的葡萄糖转运 (12)。除此之外，Akt还可以调控细胞周期，通过抑制GSK-3β，从而调控其下游的cyclin D1 的磷酸化和降解 (14)，或者负向调控cyclin依赖的激酶抑制因子 p27 Kip (15) and p21 Waf1/CIP1 (16)。Akt 也可以通过直接磷酸化mTOR，以包含raptor的雷帕霉素敏感复合体调控细胞的生长(17)。更重要的是，Akt磷酸化和抑制TSC2， 而TSC2在 mTOR-raptor 复合体中是mTOR的抑制因子(18,19)。

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3. Franke, T.F. et al. (1995) Cell 81, 727-36.
4. Alessi, D.R. et al. (1996) EMBO J 15, 6541-51.
5. Sarbassov, D.D. et al. (2005) Science 307, 1098-101.
6. Jacinto, E. et al. (2006) Cell 127, 125-37.
7. Cardone, M.H. et al. (1998) Science 282, 1318-21.
8. Brunet, A. et al. (1999) Cell 96, 857-68.
9. Zimmermann, S. and Moelling, K. (1999) Science 286, 1741-4.
10. Cantley, L.C. and Neel, B.G. (1999) Proc Natl Acad Sci USA 96, 4240-5.
11. Vlahos, C.J. et al. (1994) J Biol Chem 269, 5241-8.
12. Hajduch, E. et al. (2001) FEBS Lett 492, 199-203.
13. Cross, D.A. et al. (1995) Nature 378, 785-9.
14. Diehl, J.A. et al. (1998) Genes Dev 12, 3499-511.
15. Gesbert, F. et al. (2000) J Biol Chem 275, 39223-30.
16. Zhou, B.P. et al. (2001) Nat Cell Biol 3, 245-52.
17. Navé, B.T. et al. (1999) Biochem J 344 Pt 2, 427-31.
18. Inoki, K. et al. (2002) Nat Cell Biol 4, 648-57.
19. Manning, B.D. et al. (2002) Mol Cell 10, 151-62.

Application References

• Gray, M.J. et al. (2008) J Natl Cancer Inst 100, 109-20.Applications:Western Blotting
• Fos, C. et al. (2008) J Immunol 181, 1969-77.Applications:Western Blotting
• Engelman, J.A. et al. (2008) Nat Med 14, 1351-6.Applications:IHC-P (paraffin)
• Guertin, D.A. et al. (2009) Cancer Cell 15, 148-59.Applications:IHC-P (paraffin),Western Blotting
• Allard, D. et al. (2008) J Biol Chem 283, 19739-47.Applications:IHC-P (paraffin)
• De Raedt, T. et al. (2011) Cancer Cell 20, 400-13.Applications:Western Blotting
• Kleiman, L.B. et al. (2011) Mol Cell 43, 723-37.Applications:Western Blotting
• Sykes, S.M. et al. (2011) Cell 146, 697-708.Applications:Flow Cytometry
• Cheung, R. et al. (2011) J Clin Invest 121, 4446-61.Applications:Western Blotting
• Siemens, N. et al. (2011) J Biol Chem 286, 21612-22.Applications:Western Blotting
• Lan, R. et al. (2012) Am J Physiol Renal Physiol 302, F1210-23.Applications:IHC-P (paraffin)
• Matsuura, S. et al. (2012) Blood 119, 3155-63.Applications:Western Blotting
• Jothi, M. et al. (2012) Cell Cycle 11, 895-908.Applications:Western Blotting
• Yoshioka, K. et al. (2012) Nat Med 18, 1560-9.Applications:Western Blotting
• Sourbier, C. et al. (2013) Cancer Cell 23, 228-37.Applications:Western Blotting
• Sasaki, M. et al. (2011) Nat Med 17, 944-51.Applications:Western Blotting
• Liu, P. et al. (2014) Nature 508, 541-5.Applications:IHC-P (paraffin)

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Protocols

4060 :

Western Blotting Immunoprecipitation (Magnetic) Immunohistochemistry (Paraffin) Flow Immunofluorescence Immunohistochemistry (Frozen)

Companion Products

• 1140 Phospho-Akt (Ser473) Blocking Peptide
• 12630 SignalFire™ Plus ECL Reagent
• 12694 Phospho-Akt (Ser473) (D9W9U) Mouse mAb
• 12757 SignalFire™ Elite ECL Reagent
• 2964 Akt2 (5B5) Rabbit mAb
• 2965 Phospho-Akt (Thr308) (C31E5E) Rabbit mAb
• 2967 Akt1 (2H10) Mouse mAb
• 3788 Akt3 (62A8) Rabbit mAb
• 4071 Phospho-Akt (Ser473) (D9E) XP^® Rabbit mAb (Alexa Fluor^® 488 Conjugate)
• 4075 Phospho-Akt (Ser473) (D9E) XP^® Rabbit mAb (Alexa Fluor^® 647 Conjugate)
• 4691 Akt (pan) (C67E7) Rabbit mAb
• 6883 SignalFire™ ECL Reagent
• 7074 Anti-rabbit IgG, HRP-linked Antibody
• 7727 Biotinylated Protein Ladder Detection Pack
• 8101 SignalSlide^® Phospho-Akt (Ser473) IHC Controls
• 8112 SignalStain^® Antibody Diluent
• 8114 SignalStain^® Boost IHC Detection Reagent (HRP, Rabbit)
• 8200 PhosphoPlus^® Akt (Ser473) Antibody Duet
• 9272 Akt Antibody
• 9916 Phospho-Akt Pathway Antibody Sampler Kit