Induction of thymidine kinases in phytohaemagglutinin-stimulated human lymphocytes

Munch-Petersen, B; Tyrsted, Gerda

doi:10.1016/0005-2787(77)90152-6

Cited by 68 publications

(16 citation statements)

References 25 publications

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“…2B), indicating that dNK activities were not limited to a specific cell tissue or developmental stage. The low thymidine kinase activity in the developing cells and tissues was unexpected compared to the mammalian cells, which have high TK1 activity in dividing cells [22][23][24]. The dNK in the fruit fly is also cell cycle regulated, although the demand for dNTPs and the regulation of the nucleotide pool in plants is apparently different from that in mammals [25].…”

Section: Discussionmentioning

confidence: 99%

Two thymidine kinases and one multisubstrate deoxyribonucleoside kinase salvage DNA precursors in Arabidopsis thaliana

et al. 2012

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Deoxyribonucleotides are the building blocks of DNA and can be synthesized via de novo and salvage pathways. Deoxyribonucleoside kinases (http://www.chem.qmul.ac.uk/iubmb/enzyme/EC2/7/1/145.html) salvage deoxyribonucleosides by transfer of a phosphate group to the 5′ of a deoxyribonucleoside. This salvage pathway is well characterized in mammals, but in contrast, little is known about how plants salvage deoxyribonucleosides. We show that during salvage, deoxyribonucleosides can be phosphorylated by extracts of Arabidopsis thaliana into corresponding monophosphate compounds with an unexpected preference for purines over pyrimidines. Deoxyribonucleoside kinase activities were present in all tissues during all growth stages. In the A. thaliana genome, we identified two types of genes that could encode enzymes which are involved in the salvage of deoxyribonucleosides. Thymidine kinase activity was encoded by two thymidine kinase 1 (http://www.chem.qmul.ac.uk/iubmb/enzyme/EC2/7/1/21.html)‐like genes (AtTK1a and AtTK1b). Deoxyadenosine, deoxyguanosine and deoxycytidine kinase activities were encoded by a single AtdNK gene. T‐DNA insertion lines of AtTK1a and AtTK1b mutant genes had normal growth, although AtTK1a AtTK1b double mutants died at an early stage, which indicates that AtTK1a and AtTK1b catalyze redundant reactions. The results obtained in the present study suggest a crucial role for the salvage of thymidine during early plant development. Database Sequence data from the present study have been deposited in the EMBL database/GenBank under accession numbers: http://www.ebi.ac.uk/gxa/gene/AT3G07800 (AtTK1a), http://www.ebi.ac.uk/gxa/gene/AT5G23070 (AtTK1b) and http://www.ebi.ac.uk/gxa/gene/AT1G72040 (AtdNK).

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Section: Discussionmentioning

confidence: 99%

Two thymidine kinases and one multisubstrate deoxyribonucleoside kinase salvage DNA precursors in Arabidopsis thaliana

et al. 2012

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“…It has a narrow specificity, phosphorylates only deoxythymidine (dT) and deoxyuridine, and is strictly cell-cycleregulated. TK1 activity is low or absent in resting cells, starts to occur in late G 1 cells, increases in S phase (coinciding with the increase in DNA synthesis), and disappears during mitosis (3)(4)(5)(6).…”

mentioning

confidence: 99%

Structures of thymidine kinase 1 of human and mycoplasmic origin

Welin

Kosinska

Mikkelsen

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

117

167

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Cytosolic thymidine kinase 1, TK1, is a well known cell-cycleregulated enzyme of importance in nucleotide metabolism as well as an activator of antiviral and anticancer drugs such as 3-azido-3-deoxythymidine (AZT). We have now determined the structures of the TK1 family, the human and Ureaplasma urealyticum enzymes, in complex with the feedback inhibitor dTTP. The TK1s have a tetrameric structure in which each subunit contains an ␣͞␤-domain that is similar to ATPase domains of members of the RecA structural family and a domain containing a structural zinc. The zinc ion connects ␤-structures at the root of a ␤-ribbon that forms a stem that widens to a lasso-type loop. The thymidine of dTTP is hydrogen-bonded to main-chain atoms predominantly coming from the lasso loop. This binding is in contrast to other deoxyribonucleoside kinases where specific interactions occur with side chains. The TK1 structure differs fundamentally from the structures of the other deoxyribonucleoside kinases, indicating a different evolutionary origin.crystal structures ͉ deoxynucleotide metabolism ͉ prodrug activation

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“…In eukaryotic cells, there are two TK isoenzymes: TK1 and TK2, also called cytosolic and mitochondrial TK, respectively. The amount of cytosolic TK1 is increased significantly in cells during transition from G 1 to S phase (1,2), whereas the expression level of TK2 is low and is controlled in a cell cycle-independent manner (3,4). TK1 is highly expressed in dividing or malignant cells, but is absent in quiescent cells (5)(6)(7)(8), and its expression is stringently regulated in normal cells, but not in malignant cells (9,10).…”

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confidence: 99%

Serine 13 Is the Site of Mitotic Phosphorylation of Human Thymidine Kinase

Chang¹,

Huang²,

Chi³

1998

Journal of Biological Chemistry

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Thymidine kinase (TK) 1 is an enzyme that catalyzes the transfer of the terminal phosphate of ATP to the 5Ј-hydroxyl group of thymidine to form dTMP, which is the salvage pathway for dTTP synthesis. In eukaryotic cells, there are two TK isoenzymes: TK1 and TK2, also called cytosolic and mitochondrial TK, respectively. The amount of cytosolic TK1 is increased significantly in cells during transition from G 1 to S phase (1, 2), whereas the expression level of TK2 is low and is controlled in a cell cycle-independent manner (3, 4). TK1 is highly expressed in dividing or malignant cells, but is absent in quiescent cells (5-8), and its expression is stringently regulated in normal cells, but not in malignant cells (9, 10).Studies on TK1 regulation have provided a good model for understanding the molecular events that coordinate progression through the cell cycle. It is well documented that the transcriptional and translational activation of TK1 gene expression leads to elevation of its activity in the G 1 /S phase (11-18). In addition, other lines of evidence have shown that the C-terminal region of the TK1 polypeptide may determine its stability in cells in different growth states, indicating that cell cycle-dependent degradation is also involved in the regulation of TK1 expression (19 -21). Thus, it is clear that multiple levels of control regulate TK1 expression in eukaryotic cells.Our laboratory has previously reported that TK1 can be phosphorylated in human promyeloleukemia cells in response to growth stimulation (22). The phosphorylated form of TK1 was also detetected by isoelectric focusing gel analysis of TK1 purified from mouse Ehrlich ascites tumor cells (23). The regulation of TK1 phosphorylation was investigated further during the cell cycle. When cells were M phase-arrested by treatment with nocodazole, a microtubule-depolymerizing drug, TK1 became hyperphosphorylated in K562, and HeLa cells (24). Phosphoaminoacid analysis of immunoprecipitated human TK1 polypeptide indicated that serine is the residue involved in mitotic phosphorylation (22,24). Amino acid sequence analysis reveals that several potential phosphorylation sites exist for a variety of serine/threonine protein kinases, including cAMP-dependent protein kinase at serine 194, cyclindependent kinase(s) at serine 13 and serine 231, and protein kinase C at serine 30. In this study, we examined the specific phosphorylated site for human TK1 in mitotically arrested TK-deficient mouse Ltk Ϫ fibroblasts and human carcinoma HeLa cells, and we identified the kinase responsible for the mitotic phosphorylation of hTK1. The physiologic role of the mitotic phosphorylation of hTK1 was also investigated.

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Induction of thymidine kinases in phytohaemagglutinin-stimulated human lymphocytes

Cited by 68 publications

References 25 publications

Two thymidine kinases and one multisubstrate deoxyribonucleoside kinase salvage DNA precursors in Arabidopsis thaliana

Two thymidine kinases and one multisubstrate deoxyribonucleoside kinase salvage DNA precursors in Arabidopsis thaliana

Structures of thymidine kinase 1 of human and mycoplasmic origin

Serine 13 Is the Site of Mitotic Phosphorylation of Human Thymidine Kinase

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