Open AccessMalaria Protein Kinase CK2 (PfCK2) Shows Novel Mechanisms of Regulation
Author(s) -
Michele Graciotti,
Mahmood M. Alam,
Lev Solyakov,
Ralf Schmid,
Glenn A. Burley,
Andrew R. Bottrill,
Christian Doerig,
Paul M. Cullis,
Andrew B. Tobin
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0085391
Subject(s) - casein kinase 2 , ask1 , cyclin dependent kinase 9 , map2k7 , mitogen activated protein kinase kinase , map kinase kinase kinase , biology , microbiology and biotechnology , cyclin dependent kinase 2 , phosphorylation , protein kinase a , biochemistry , kinase
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.