Cell Signaling Technology

Product Pathways - PI3K / Akt Signaling

Hamartin/TSC1 (D43E2) Rabbit mAb #6935

Applications Reactivity Sensitivity MW (kDa) Isotype
W IP H M R Endogenous 150-170 Rabbit IgG

Applications Key:  W=Western Blotting  IP=Immunoprecipitation
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

Hamartin/TSC1 (D43E2) Rabbit mAb recognizes endogenous levels of total TSC1 protein.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Val640 of human TSC1.

Western Blotting

Western Blotting

Western blot analysis of extracts from wild type and TSC1 -/- MEF cells, HT-1080, and Rat2 cells using Hamartin/TSC1 (D43E2) Rabbit mAb.

Background

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that causes symptoms including hamartomas in brain, kidney, heart, lung and skin (1). The tumor suppressor genes TSC1 and TSC2 encode hamartin and tuberin, respectively (2,3). Hamartin and tuberin form a functional complex and are involved in numerous cellular activities such as vesicular trafficking, regulation of the G1 phase of the cell cycle, steroid hormone regulation, Rho activation and anchoring neuronal intermediate filaments to the actin cytoskeleton (4-9). The combination of genetic, biochemical and cell-biological studies demonstrate that the tuberin/hamartin complex functions as a GTPase-activating protein for the Ras-related small G protein Rheb and thus inhibits targets of rapamycin including mTOR. Cells lacking hamartin or tuberin fail to inhibit phosphorylation of S6 kinase resulting in the activation of S6 ribosomal protein's translation of 5'TOP mRNA transcripts (10). Hamartin is phosphorylated by CDK1 (cdc2) at Thr417, Ser584 and Thr1047 in cells in G2/M phase of the cell cycle (11).

  1. Sparagana, S.P. and Roach, E.S. (2000) Curr. Opin. Neurol. 13, 115-119.
  2. van Slegtenhorst, M. et al. (1997) Science 277, 805-808.
  3. No authors listed. (1993) Cell 75, 1305-1315.
  4. Plank, T.L. et al. (1998) Cancer Res. 58, 4766-4770.
  5. Xiao, G. et al. (1997) J. Biol. Chem. 272, 6097-6100.
  6. Tapon, N. et al. (2001) Cell 105, 345-355.
  7. Henry, K.W. et al. (1998) J. Biol. Chem. 273, 20535-20539.
  8. Lamb, R.F. et al. (2000) Nat. Cell Biol. 2, 281-287.
  9. Haddad, L.A. et al. (2002) J. Biol. Chem. 277, 44180-44186.
  10. Manning, B.D. and Cantley, L.C. (2003) Trends Biochem Sci. 28, 573-576.
  11. Astrinidis, A. et al. (2003) J. Biol. Chem. 278, 51372-51379.

Application References

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

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