Product Pathways - PI3K / Akt Signaling
Phospho-Tuberin/TSC2 (Thr1462) Antibody #3611
|3611S||100 µl (10 western blots)||---||In Stock||---|
|3611||carrier free and custom formulation / quantity||email request|
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Species cross-reactivity is determined by western blot.
Applications Key: W=Western Blotting
Species predicted to react based on 100% sequence homology: Rat.
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 animals with a synthetic phosphopeptide corresponding to residues surrounding Thr1462 of human tuberin. Antibodies are purified by protein A and peptide affinity chromatography.
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).
Tuberin is a product of the TSC2 tumor suppressor gene and an important regulator of cell proliferation and tumor development (1). Mutations in either TSC2 or the related TSC1 (hamartin) gene cause tuberous sclerosis complex (TSC), an autosomal dominant disorder characterized by development of multiple, widespread non-malignant tumors (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). In addition, tuberin inhibits the mammalian target of rapamycin (mTOR), which promotes inhibition of p70 S6 kinase, activation of eukaryotic initiation factor 4E binding protein 1 (4E-BP1, an inhibitor of translation initiation), and eventual inhibition of 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).
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- 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.A. et al. (2002) J. Biol. Chem. 277, 30958-30967.
- Inoki, K. et al. (2002) Nat. Cell Biol. 4, 648-657.
- 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.
- Manning, B.D. et al. (2002) Mol Cell 10, 151-62. Applications: Western Blotting.
- Andreozzi, F. et al. (2004) Endocrinology 145, 2845-57. Applications: Western Blotting.
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