Kinase activity of casein kinase 1 delta (CK1δ) is modulated by protein kinase C α (PKCα) by site-specific phosphorylation within the kinase domain of CK1δ.

08:00 EDT 13th May 2019 | BioPortfolio

Summary of "Kinase activity of casein kinase 1 delta (CK1δ) is modulated by protein kinase C α (PKCα) by site-specific phosphorylation within the kinase domain of CK1δ."

Members of the casein kinase 1 (CK1) family are involved in regulation of crucial cellular pathways including chromosomal segregation, DNA repair, and apoptosis. Therefore, the activity of CK1 isoforms needs to be tightly regulated in order to avoid pathogenesis of proliferative diseases. Regulation of cellular CK1 activity is mainly mediated by (auto-) phosphorylation within its C-terminal regulatory domain. Cellular kinases, among them protein kinase A (PKA), checkpoint kinase 1 (Chk1), protein kinase C α (PKCα), and cyclin-dependent kinases (CDKs) have already been identified to C-terminally phosphorylate CK1δ, thereby modulating its kinase activity. In the present study we analyzed the CK1δ kinase domain for phosphorylation sites targeted by PKCα. Several phosphorylation sites were identified in vitro by initially using GST-CK1δ wild type and phosphorylation-site mutant protein fragments originating from the CK1δ kinase domain. Residues S53, T176, and S181 could finally be confirmed as targets for PKCα. Determination of kinetic parameters of full-length wild type and mutant GST-CK1δ-mediated substrate phosphorylation revealed that integrity of residue T176 is crucial for maintaining CK1δ kinase activity. Functional biochemical and cell culture-based analysis discovered that site-specific phosphorylation of CK1δ by PKCα contributes to fine-tuning of CK1δ kinase activity. In summary, our work for the first time demonstrates the effects of PKCα-mediated site-specific phosphorylation in the CK1δ kinase domain and enhances our knowledge about the regulation of the disease-associated CK1 kinase family.


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This article was published in the following journal.

Name: Biochimica et biophysica acta. Proteins and proteomics
ISSN: 1878-1454


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Medical and Biotech [MESH] Definitions

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A casein kinase I isoenzyme that plays a role in intracellular signaling pathways including the CELL CYCLE, membrane trafficking, and RNA processing. In DROSOPHILA casein kinase Ialpha has been in regulation of Hedghog and Wingless signaling pathways. Multiple isoforms of casein kinase Ialpha exist and are due ALTERNATIVE SPLICING.

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A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.

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