Cell Signaling Technology

Product Pathways - PI3K / 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. Species enclosed in parentheses are predicted to react based on 100% sequence homology.

Protocols

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 Blotting

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 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).

  1. Soucek, T. et al. (1998) Proc. Natl. Acad. Sci. USA 95, 15653-15658.
  2. Sparagana, S.P. and Roach, E.S. (2000) Curr. Opin. Neurol. 13, 115-119.
  3. Manning, B. D. et al. (2002) Mol. Cell 10, 151-161.
  4. Aicher, L. D. et al. (2001) J. Biol. Chem. 276, 21017-21021.
  5. Dan, H. C. et al. (2002) J. Biol. Chem. 277, 35364-35370.
  6. Goncharova, E.A. et al. (2002) J. Biol. Chem. 277, 30958-30967.
  7. Inoki, K. et al. (2002) Nat. Cell Biol. 4, 648-657.
  8. Gao, X. and Pan, D. (2001) Genes Dev. 15, 1383-1392.
  9. Potter, C. J. et al. (2001) Cell 105, 357-368.
  10. Tapon, N. et al. (2001) Cell 105, 345-355.

Application References

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For Research Use Only. Not For Use In Diagnostic Procedures.

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