ArticleMolecular cell2022
Kinase domain autophosphorylation rewires the activity and substrate specificity of CK1 enzymes.
Article in Molecular cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 34 citations in OpenAlex.
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- Proteomic Snapshots of Structural Cross-Linking Rearrangements in CaJournal of proteome research · 2026Article
- Disordered but rhythmic-the role of intrinsic protein disorder in eukaryotic circadian timing.FEBS letters · 2026Review
- The mitotic functions of a fission yeast CK1 enzyme are regulated by Cdk1-dependent and auto-phosphorylation.The Journal of biological chemistry · 2026Article
- Article
- Dual-specific autophosphorylation of kinase IKK2 enables phosphorylation of substrate IκBα through a phosphoenzyme intermediate.bioRxiv : the preprint server for biology · 2025Article
- CDK1-mediated phosphorylation of USP37 regulates SND1 stability and promotes oncogenesis in colorectal cancer.Acta pharmaceutica Sinica. B · 2025Article
- Wnt signaling inhibits casein kinase 1α activity by modulating its interaction with protein phosphatase 2A.Cell reports · 2025Article
- A bi-kinase module sensitizes and potentiates plant immune signaling.Science advances · 2025Article
- Structural and functional effects of phosphopriming and scaffolding in the kinase GSK-3β.Science signaling · 2024Article
- Casein Kinase 1α-A Target for Prostate Cancer Therapy?Cancers · 2024Review
- CK1 and PP1 regulate Rift Valley fever virus genome replication through L protein phosphorylation.Antiviral research · 2024Article
- Substrate displacement of CK1 C-termini regulates kinase specificity.Science advances · 2024Article
- The DNA Damage Repair Function of Fission Yeast CK1 Involves Targeting Arp8, a Subunit of the INO80 Chromatin Remodeling Complex.Molecular and cellular biology · 2024Article
- Circadian rhythms in the Drosophila eye may regulate adaptation of vision to light intensity.Frontiers in neuroscience · 2024Article
- Fuzzy interactions between the auto-phosphorylated C-terminus and the kinase domain of CK1δ inhibits activation of TAp63α.Scientific reports · 2023Article
- Structure-Based Development of Isoform-Selective Inhibitors of Casein Kinase 1ε vs Casein Kinase 1δ.Journal of medicinal chemistry · 2023Article
- PERIOD phosphorylation leads to feedback inhibition of CK1 activity to control circadian period.Molecular cell · 2023Article
- Evolution of casein kinase 1 and functional analysis of newFrontiers in physiology · 2022Article
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
CK1s are acidophilic serine/threonine kinases with multiple critical cellular functions; their misregulation contributes to cancer, neurodegenerative diseases, and sleep phase disorders. Here, we describe an evolutionarily conserved mechanism of CK1 activity: autophosphorylation of a threonine (T220 in human CK1δ) located at the N terminus of helix αG, proximal to the substrate binding cleft. Crystal structures and molecular dynamics simulations uncovered inherent plasticity in αG that increased upon T220 autophosphorylation. The phosphorylation-induced structural changes significantly altered the conformation of the substrate binding cleft, affecting substrate specificity. In T220 phosphorylated yeast and human CK1s, activity toward many substrates was decreased, but we also identified a high-affinity substrate that was phosphorylated more rapidly, and quantitative phosphoproteomics revealed that disrupting T220 autophosphorylation rewired CK1 signaling in Schizosaccharomyces pombe. T220 is present exclusively in the CK1 family, thus its autophosphorylation may have evolved as a unique regulatory mechanism for this important family.
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