Cell Signaling Technology

Product Pathways - Cell Cycle / Checkpoint

TTK Antibody #3255

Applications Reactivity Sensitivity MW (kDa) Source
W IP IF-IC H (Mk) Endogenous 95 Rabbit

Applications Key:  W=Western Blotting  IP=Immunoprecipitation  IF-IC=Immunofluorescence (Immunocytochemistry)
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 Antibody detects endogenous levels of total TTK protein. TTK, also known as PYT (Phosphotyrosine Picked Threonine Kinase), is the human homolog of MSP1 (Monopolar Spindle 1) in budding yeast and murine ESK (Embryonal Carcinoma STY Kinase).

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Glu137 of human TTK. Antibodies were purified by affinity chromatography.

Western Blotting

Western Blotting

Western blot analysis of recombinant GST-TTK (#7655) and extracts from OVCAR8 and K562 cell lines using TTK Antibody.

IF-IC

IF-IC

Confocal immunofluorescent analysis of OVCAR8 cells using TTK Antibody showing nuclear localization.

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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