Cell Signaling Technology

Product Pathways - Cell Cycle / Checkpoint

TTK Kinase #7655

Cell Signaling Technology offers a full line of protein kinases, substrates, antibody detection reagents and HTScan® kits. Browse our "Reagents for High-Throughput Screening" product listing or contact us at drugdiscovery@cellsignal.com.

Description

Purified recombinant kinase, supplied as a GST fusion protein.

Source / Purification

This GST-kinase fusion protein was produced using a baculovirus expression system with a construct expressing the kinase with an amino terminal GST tag. The protein was purified by one-step affinity chromatography using glutathione-agarose.

Quality Control

The purified kinase fusion protein was quality controlled for purity using SDS-PAGE followed by Coomassie or silver stain and Western blot. The specific activity of the kinase was determined using a radiometric assay.

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 and TTK may present a 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

This product is for in vitro research use only and is not intended for use in humans or animals. This product is not intended for use as therapeutic or in diagnostic procedures.

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