Site-Directed Mutagenesis in the Research of Protein Kinases - The Case of Protein Kinase CK2

Sajnaga, Ewa; Szyszka, Ryszard; Kubiński, Konrad

doi:10.5772/54873

Cited by 3 publications

(3 citation statements)

References 156 publications

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“…Interestingly, both missense variants are located in the KEN box-like motif of CK2β (32-DKFNLTGLN-40), which is known to participate in cell-cycle-dependent protein degradation in other kinases. 63 The exact role of the KEN box for CK2β has not been characterized yet, but considering its close proximity to the destruction box (attributed for proteasome degradation), it is likely to play a similar role in CK2 as in other kinases. In addition, the CK2β residues from position 20 to 33 are already known to be crucial for its function as an ectokinase.…”

Section: Discussionmentioning

confidence: 99%

De novo variants of CSNK2B cause a new intellectual disability-craniodigital syndrome by disrupting the canonical Wnt signaling pathway

Asif

Kaygusuz

Shinawi

et al. 2022

Human Genetics and Genomics Advances

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Section: Discussionmentioning

confidence: 99%

De novo variants of CSNK2B cause a new intellectual disability-craniodigital syndrome by disrupting the canonical Wnt signaling pathway

Asif

Kaygusuz

Shinawi

et al. 2022

Human Genetics and Genomics Advances

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“…We chose to investigate the ectokinase CK2α due to the established cancer-association of CK2 [24][25][26][27] and the amenability of the kinase to protein engineering for developing a proof-ofconcept ectophosphoproteomic workflow. 19,28 We engineered cell-tethered forms of CK2α, which were more efficient in surface phosphorylation in vitro than the free enzyme. We used ATP-gamma-thiophosphate (ATPγS) as a chemical reporter to probe the surface substrates of CK2α, identifying and validating substrates, including CD44, by mass spectrometry and by Western blot.…”

Section: Introductionmentioning

confidence: 99%

“…We chose to investigate the ectokinase CK2α due to the established cancer-association of CK2 24–27 and the amenability of the kinase to protein engineering for developing a proof-of-concept ectophosphoproteomic workflow. 19,28…”

Section: Introductionmentioning

confidence: 99%

Chemoproteomics reveals immunogenic and tumor-associated cell surface substrates of ectokinase CK2α

Delaveris,

Kong,

Glasgow

et al. 2024

Preprint

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New epitopes for immune recognition provide the basis of anticancer immunity. Due to the high concentration of extracellular adenosine triphosphate in the tumor microenvironment, we hypothesized that extracellular kinases (ectokinases) could have dysregulated activity and introduce aberrant phosphorylation sites on cell surface proteins. We engineered a cell-tethered version of the extracellular kinase CK2α, demonstrated it was active on cells under tumor-relevant conditions, and profiled its substrate scope using a chemoproteomic workflow. We then demonstrated that mice developed polyreactive antisera in response to syngeneic tumor cells that had been subjected to surface hyperphosphorylation with CK2α. Interestingly, these mice developed B cell and CD4+ T cell responses in response to these antigens but failed to develop a CD8+ T cell response. This work provides a workflow for probing the extracellular phosphoproteome and demonstrates that extracellular phosphoproteins are immunogenic even in a syngeneic system.

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Structure-Guided Discovery of Adenosine Triphosphate-Competitive Casein Kinase 2 Inhibitors

et al. 2023

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Casein kinase 2 (CK2) is a ubiquitous, highly pleiotropic serine-threonine kinase. CK2 has been identified as a potential drug target for the treatment of cancer and related disorders. Several adenosine triphosphate-competitive CK2 inhibitors have been identified and have progressed at different levels of clinical trials. This review presents details of CK2 protein, structural insights into adenosine triphosphate binding pocket, current clinical trial candidates and their analogues. Further, it includes the emerging structure-based drug design approaches, chemistry, structure–activity relationship and biological screening of potent and selective CK2 inhibitors. The authors tabulated the details of CK2 co-crystal structures because these co-crystal structures facilitated the structure-guided discovery of CK2 inhibitors. The narrow hinge pocket compared with related kinases provides useful insights into the discovery of CK2 inhibitors.

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Site-Directed Mutagenesis in the Research of Protein Kinases - The Case of Protein Kinase CK2

Cited by 3 publications

References 156 publications

De novo variants of CSNK2B cause a new intellectual disability-craniodigital syndrome by disrupting the canonical Wnt signaling pathway

De novo variants of CSNK2B cause a new intellectual disability-craniodigital syndrome by disrupting the canonical Wnt signaling pathway

Chemoproteomics reveals immunogenic and tumor-associated cell surface substrates of ectokinase CK2α

Structure-Guided Discovery of Adenosine Triphosphate-Competitive Casein Kinase 2 Inhibitors

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