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Cell-based readouts of copper-modulated CK2 kinase activity
Thesis   Open access

Cell-based readouts of copper-modulated CK2 kinase activity

Rongrong Li
Master of Science (M.S.), Drexel University
Jul 2021
DOI:
https://doi.org/10.17918/00000849
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Abstract

Copper Protein kinase CK2
Casein kinase 2 (CK2) is a heterotetrameric serine/threonine kinase that phosphorylates hundreds of substrates to regulate diverse cellular processes ranging from signal transduction to cell cycle progression and cell proliferation. In addition to its high degree of promiscuity, another unusual characteristic of CK2 is its apparent constitutive activity: in contrast to the tight regulation seen in most other kinases, no definitive mechanism for regulating CK2 kinase activity has been defined. An emerging paradigm in kinase biology is regulation of catalytic activity by binding to copper. Indeed, the MAPK pathway kinases MEK1/2 and the autophagic kinase Ulk1/2 are copper-dependent, and data from our lab indicates that CK2 is likewise a copper-modulated kinase. Here we have employed a pharmacological approach to investigate the role of copper in regulating CK2 kinase activity in human cancer cells. We show that Cu-ATSM, a cell-permeable copper compound, enhances CK2 kinase activity in vitro and in cells as assessed by Western blotting using phospho-specific antibodies to monitor CK2 catalytic activity. Moreover, we observed phosphorylation of the catalytic [alpha] subunit of CK2 in response to increased intracellular copper. Collectively, these results demonstrate that copper plays a role in modulating CK2 kinase activity in cells and suggests a possible regulatory mechanism of CK2 kinase activity through copper-induced catalytic [alpha] subunit phosphorylation.

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