Product Pathways - Akt Signaling
Phospho-Tuberin/TSC2 (Thr1462) Antibody #3611
| Applications | Reactivity | Sensitivity | MW (kDa) | Source |
|---|---|---|---|---|
| W | H M (R) | Endogenous | 200 | Rabbit |
Applications Key:
W=Western Blotting
Reactivity Key:
H=Human
M=Mouse
R=Rat
Species cross-reactivity is determined by Western blot.
Specificity / Sensitivity
Phospho-Tuberin/TSC2 (Thr1462) Antibody detects endogenous levels of tuberin only when phosphorylated at threonine 1462. This antibody does not detect tuberin phosphorylated at other sites.
Source / Purification
Polyclonal antibodies are produced by immunizing rabbits with a synthetic phospho-peptide (KLH-coupled) corresponding to residues surrounding Thr1462 of human tuberin. Antibodies are purified by protein A and peptide affinity chromatography.
Western Blotting
Western blot analysis of extracts from NIH/3T3 cells, untreated, PDGF-treated (50 ng/ml), PDGF and wortmannin-treated (200 nM) or PDGF and rapamycin-treated (5 nM), and MCF-7 cells, untreated or IGF-1 treated for the indicated times, using Phospho-Tuberin/TSC2 (Thr1462) Antibody (upper) or Tuberin/TSC2 Antibody #3612 (lower).
Background
Tuberin, a product of the tumor suppressor gene TSC2, is important in regulating cell proliferation and tumor development (1). Mutations in either TSC1 or TSC2 are responsible for tuberous sclerosis complex (TSC), an autosomal dominant disorder (2). Tuberin is directly phosphorylated at Thr1462 by Akt/PKB (3). Phosphorylation at Thr1462 and Tyr1571 regulates tuberin-hamartin complexes and tuberin activity (3-5). Additionally, tuberin inhibits the mammalian target of rapamycin (mTOR), resulting in inhibition of p70 S6 kinase and activation of eukaryotic initiation factor 4E binding protein 1 (4E-BP1, an inhibitor of translation initiation) and thus, inhibits translation (3,6-7).
Tuberin is phosphorylated on Ser939 and Thr1462 in response to PI3K activation, and that the human TSC complex is a direct biochemical target of the PI3K/Akt pathway (3). This data complements Drosophila genetics studies suggesting the possible involvement of the tuberin-hamartin complex in the PI3K/Akt mediated insulin pathway (8-10).
- Soucek, T. et al. (1998) Proc. Natl. Acad. Sci. USA 95, 15653-15658.
- Sparagana, S.P. and Roach, E.S. (2000) Curr. Opin. Neurol. 13, 115-119.
- Manning, B. D. et al. (2002) Mol. Cell 10, 151-161.
- Aicher, L. D. et al. (2001) J. Biol. Chem. 276, 21017-21021.
- Dan, H. C. et al. (2002) J. Biol. Chem. 277, 35364-35370.
- Goncharova, E. et al. (2002) J. Biol. Chem. 277, 30958-30967.
- Gao, X. and Pan, D. (2001) Genes Dev. 15, 1383-1392.
- Potter, C. J. et al. (2001) Cell 105, 357-368.
- Tapon, N. et al. (2001) Cell 105, 345-355.
Application References
- Manning, B. D. et al. (2002) Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway. Mol. Cell 10, 151-162. This article references the use of Phospho-Tuberin/TSC2 (Thr1462) Antibody in the following applications: Western Blotting
- Andreozzi, F. et al. (2004) Activation of the hexosamine pathway leads to phosphorylation of insulin receptor substrate-1 on Ser307 and Ser612 and impairs the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin insulin biosynthetic pathway in RIN pancreatic beta-cells. This article references the use of Phospho-Tuberin/TSC2 (Thr1462) Antibody in the following applications: Western Blotting
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Companion Products
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This product is for in vitro research use only and is not intended for use in humans or animals. This product is not intended for use as therapeutic or in diagnostic procedures.