Cell Signaling Technology

Product Pathways - PI3K / Akt Signaling

Phospho-Tuberin/TSC2 (Ser1254) Antibody #3616

Applications Reactivity Sensitivity MW (kDa) Source
W M R (H) 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 (Ser1254) Antibody detects endogenous levels of tuberin only when phosphorylated at serine 1254. 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 Ser1254 of human tuberin. Antibodies are purified by protein A and peptide affinity chromatography.

Western Blotting

Western Blotting

Western blot analysis of extracts from CAD and PC12 cells, using Phospho-Tuberin/TSC2 (Ser1254) Antibody. The phospho-specificity of the antibody was verified by treating the membrane with (+) or without (-) calf intestinal phosphatase (CIP) after Western transfer.

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).

p38-activated kinase MK2 (MAPKAPK-2) phosphorylates Ser1254 of tuberin, and thus augments the interaction between tuberin and 14-3-3 (8).

  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. Li, Y. et al. (2003) J. Biol. Chem. 278, 13663-13671.

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