Cell Signaling Technology

Product Pathways - Cell Cycle / Checkpoint

TTK (D15B7) Rabbit mAb #5469

Applications Reactivity Sensitivity MW (kDa) Isotype
W IP H (Mk) Endogenous 95 Rabbit IgG

Applications Key:  W=Western Blotting  IP=Immunoprecipitation
Reactivity Key:  H=Human  Mk=Monkey
Species cross-reactivity is determined by western blot. Species enclosed in parentheses are predicted to react based on 100% sequence homology.

Protocols

Specificity / Sensitivity

TTK (D15B7) Rabbit mAb detects endogenous levels of total TTK protein. A background band of unknown origin is detected at 70 kDa.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to a region surrounding Ala560 of human TTK protein.

Western Blotting

Western Blotting

Western blot analysis of extracts from UT7, Ramos, and HEL cells using TTK (D15B7) Rabbit mAb.

Western Blotting

Western Blotting

Western blot analysis of extracts from HeLa cells, untreated or aphidicolin-treated (10 μg/ml; overnight), using TTK (D15B7) Rabbit mAb.

Background

TTK (Mps1, PYT) is a cell cycle regulated dual specificity kinase present in rapidly proliferating tissues and cell lines (1-3). TTK localizes to kinetochores and centromeres and is an essential component of the mitotic spindle checkpoint as well as centrosome duplication (4-6). The mitotic checkpoint inhibits entry into anaphase until all chromosomes are attached to the spindle; inhibition of this process leads to genomic instability and tumorigenesis. Phosphorylation of the BLM helicase at Ser144 by TTK maintains chromosome stability during mitosis (7). Small molecule inhibitors of TTK can block the spindle checkpoint response, thereby making TTK a potential therapeutic target (8,9).TTK also participates in the DNA damage response by directly phosphorylating and activating the cell cycle checkpoint kinase Chk2 at Thr68. Two targets phosphorylated by Chk2 are the cell cycle phosphatase cdc25 and the transcription factor p53. Inactivation of cdc25 phosphatase results in the accumulation of inactive cyclin B and cell cycle arrest following DNA damage. Phosphorylation of p53 by active Chk2 stabilizes the transcription factor and promotes cell cycle arrest and apoptosis in response to DNA damage (10).

  1. Mills, G.B. et al. (1992) J. Biol. Chem. 267, 16000-16006.
  2. Stucke, V.M. et al. (2002) EMBO J. 21, 1723-1732.
  3. Lindberg, R.A. et al. (1993) Oncogene 8, 351-359.
  4. Fisk, H.A. et al. (2003) Proc. Natl. Acad. Sci. USA 100, 14875-14880.
  5. Dou, Z. et al. (2003) Cell Res. 13, 443-449.
  6. Abrieu, A. et al. (2001) Cell 106, 83-93.
  7. Leng, M. et al. (2006) Proc. Natl. Acad. Sci. USA 103, 11485-11490.
  8. Schmidt, M. et al. (2005) EMBO Rep. 6, 866-872.
  9. Dorer, R.K. et al. (2005) Curr. Biol. 15, 1070-1076.
  10. Wei, J.H. et al. (2005) J. Biol. Chem. 280, 7748-7757.

Application References

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Companion Products

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

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