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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
Published on: January 7, 2013
Expression of TTK, a novel human protein kinase, is associated with cell proliferation
G B Mills1, R Schmandt, M McGill
1Oncology Research, Toronto General Hospital, Ontario, Canada.
Abstract:
We have isolated the full-length sequence for a unique human kinase, designated TTK. TTK was initially identified by screening of a T cell expression library with anti-phosphotyrosine antibodies. The kinases most closely related to TTK are the SPK1 serine, threonine and tyrosine kinase, the Pim1, PBS2, and CDC2 serine/threonine kinases, and the TIK kinase which was also identified through screening of an expression library with anti-phosphotyrosine antibodies. However, the relationships are distant with less than 25% identity. Nevertheless, TTK is highly conserved throughout phylogeny with hybridizing sequences being detected in mammals, fish, and yeast. TTK mRNA is present at relatively high levels in testis and thymus, tissues which contain a large number of proliferating cells, but is not detected in most other benign tissues. Freshly isolated cells from most malignant tumors assessed expressed TTK mRNA. As well, all rapidly proliferating cell lines tested expressed TTK mRNA. Escherichia coli expressing the complete kinase domain of TTK contain markedly elevated levels of phosphoserine and phosphothreonine as well as slightly increased levels of phosphotyrosine. Taken together, these findings suggest that expression of TTK, a previously unidentified member of the family of kinases which can phosphorylate serine, threonine, and tyrosine hydroxyamino acids, is associated with cell proliferation.
Insights
We identified a novel human kinase, TTK, which is highly conserved across species. TTK expression is linked to cell proliferation and is found in tumors and rapidly dividing cells.
Area of Science:
- Molecular Biology
- Biochemistry
- Genetics
Background:
- A unique human kinase, TTK, was identified using anti-phosphotyrosine antibodies.
- TTK shares distant homology with known serine, threonine, and tyrosine kinases.
- TTK is highly conserved across diverse species, including mammals, fish, and yeast.
Purpose of the Study:
- To characterize the novel human kinase TTK.
- To investigate the expression patterns and functional role of TTK.
Main Methods:
- Screening of a T cell expression library with anti-phosphotyrosine antibodies.
- Phylogenetic analysis to assess TTK conservation.
- mRNA expression analysis in various human tissues and cell lines.
- Functional analysis of TTK kinase domain in E. coli.
Main Results:
- TTK mRNA is highly expressed in testis and thymus, tissues with high cell proliferation.
- TTK mRNA is detected in most malignant tumors and rapidly proliferating cell lines.
- E. coli expressing TTK kinase domain showed elevated phosphoserine and phosphothreonine levels.
Conclusions:
- TTK is a novel kinase capable of phosphorylating serine, threonine, and tyrosine.
- TTK expression is associated with cell proliferation.
- TTK may play a role in cell proliferation and cancer.
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