Malaria protein kinase CK2 (PfCK2) shows novel mechanisms of regulation.
Casein kinase 2 (protein kinase CK2) is a conserved eukaryotic serine/theronine kinase with multiple substrates and roles in the regulation of cellular processes such as cellular stress, cell proliferation and apoptosis. Here we report a detailed analysis of the Plasmodium falciparum CK2, PfCK2, dem...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0085391 |
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| author | Michele Graciotti Mahmood Alam Lev Solyakov Ralf Schmid Glenn Burley Andrew R Bottrill Christian Doerig Paul Cullis Andrew B Tobin |
| author_facet | Michele Graciotti Mahmood Alam Lev Solyakov Ralf Schmid Glenn Burley Andrew R Bottrill Christian Doerig Paul Cullis Andrew B Tobin |
| author_sort | Michele Graciotti |
| collection | DOAJ |
| description | Casein kinase 2 (protein kinase CK2) is a conserved eukaryotic serine/theronine kinase with multiple substrates and roles in the regulation of cellular processes such as cellular stress, cell proliferation and apoptosis. Here we report a detailed analysis of the Plasmodium falciparum CK2, PfCK2, demonstrating that this kinase, like the mammalian orthologue, is a dual specificity kinase able to phosphorylate at both serine and tyrosine. However, unlike the human orthologue that is auto-phosphorylated on tyrosine within the activation loop, PfCK2 shows no activation loop auto-phosphorylation but rather is auto-phosphorylated at threonine 63 within subdomain I. Phosphorylation at this site in PfCK2 is shown here to regulate the intrinsic kinase activity of PfCK2. Furthermore, we generate an homology model of PfCK2 in complex with the known selective protein kinase CK2 inhibitor, quinalizarin, and in so doing identify key co-ordinating residues in the ATP binding pocket that could aid in designing selective inhibitors to PfCK2. |
| format | Article |
| id | doaj-art-fd256cc187a84d6d8bb110eff21ef99b |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-fd256cc187a84d6d8bb110eff21ef99b2025-08-20T03:11:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e8539110.1371/journal.pone.0085391Malaria protein kinase CK2 (PfCK2) shows novel mechanisms of regulation.Michele GraciottiMahmood AlamLev SolyakovRalf SchmidGlenn BurleyAndrew R BottrillChristian DoerigPaul CullisAndrew B TobinCasein kinase 2 (protein kinase CK2) is a conserved eukaryotic serine/theronine kinase with multiple substrates and roles in the regulation of cellular processes such as cellular stress, cell proliferation and apoptosis. Here we report a detailed analysis of the Plasmodium falciparum CK2, PfCK2, demonstrating that this kinase, like the mammalian orthologue, is a dual specificity kinase able to phosphorylate at both serine and tyrosine. However, unlike the human orthologue that is auto-phosphorylated on tyrosine within the activation loop, PfCK2 shows no activation loop auto-phosphorylation but rather is auto-phosphorylated at threonine 63 within subdomain I. Phosphorylation at this site in PfCK2 is shown here to regulate the intrinsic kinase activity of PfCK2. Furthermore, we generate an homology model of PfCK2 in complex with the known selective protein kinase CK2 inhibitor, quinalizarin, and in so doing identify key co-ordinating residues in the ATP binding pocket that could aid in designing selective inhibitors to PfCK2.https://doi.org/10.1371/journal.pone.0085391 |
| spellingShingle | Michele Graciotti Mahmood Alam Lev Solyakov Ralf Schmid Glenn Burley Andrew R Bottrill Christian Doerig Paul Cullis Andrew B Tobin Malaria protein kinase CK2 (PfCK2) shows novel mechanisms of regulation. PLoS ONE |
| title | Malaria protein kinase CK2 (PfCK2) shows novel mechanisms of regulation. |
| title_full | Malaria protein kinase CK2 (PfCK2) shows novel mechanisms of regulation. |
| title_fullStr | Malaria protein kinase CK2 (PfCK2) shows novel mechanisms of regulation. |
| title_full_unstemmed | Malaria protein kinase CK2 (PfCK2) shows novel mechanisms of regulation. |
| title_short | Malaria protein kinase CK2 (PfCK2) shows novel mechanisms of regulation. |
| title_sort | malaria protein kinase ck2 pfck2 shows novel mechanisms of regulation |
| url | https://doi.org/10.1371/journal.pone.0085391 |
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