casein kinase i


Summary: A casein kinase that was originally described as a monomeric enzyme with a molecular weight of 30-40 kDa. Several ISOENZYMES of casein kinase I have been found which are encoded by separate genes. Many of the casein kinase I isoenzymes have been shown to play distinctive roles in intracellular SIGNAL TRANSDUCTION.

Top Publications

  1. Yan W, Spruce L, Rosenblatt M, Kleyman T, Rubenstein R. Intracellular trafficking of a polymorphism in the COOH terminus of the alpha-subunit of the human epithelial sodium channel is modulated by casein kinase 1. Am J Physiol Renal Physiol. 2007;293:F868-76 pubmed
  2. Hirota T, Lee J, Lewis W, Zhang E, Breton G, Liu X, et al. High-throughput chemical screen identifies a novel potent modulator of cellular circadian rhythms and reveals CKI? as a clock regulatory kinase. PLoS Biol. 2010;8:e1000559 pubmed publisher
    ..Longdaysin provides novel possibilities in manipulating clock function due to its ability to simultaneously inhibit several key components of this conserved network across species. ..
  3. Wang Y, Liu T, Patel S, Jiang L, Xue C. The casein kinase I protein Cck1 regulates multiple signaling pathways and is essential for cell integrity and fungal virulence in Cryptococcus neoformans. Eukaryot Cell. 2011;10:1455-64 pubmed publisher
    ..Because the Saccharomyces cerevisiae homolog of Fbp1, Grr1, requires casein kinase I (Yck1 and Yck2) to phosphorylate its substrates, we investigated the function of casein kinase I in ..
  4. Perez D, Gil C, Martinez A. Protein kinases CK1 and CK2 as new targets for neurodegenerative diseases. Med Res Rev. 2011;31:924-54 pubmed publisher
    ..The role of these two kinases in the molecular pathology of different neurodegenerative diseases together with different chemical families that are able to more or less specifically inhibit CK1 and CK2 are discussed in this review. ..
  5. Tomishige N, Kumagai K, Kusuda J, Nishijima M, Hanada K. Casein kinase I{gamma}2 down-regulates trafficking of ceramide in the synthesis of sphingomyelin. Mol Biol Cell. 2009;20:348-57 pubmed publisher
    ..Here, we identify the gamma2 isoform of casein kinase I (CKIgamma2) as a kinase whose overexpression confers sphingomyelin-directed toxin-resistance to Chinese ..
  6. Babu P, Deschenes R, Robinson L. Akr1p-dependent palmitoylation of Yck2p yeast casein kinase 1 is necessary and sufficient for plasma membrane targeting. J Biol Chem. 2004;279:27138-47 pubmed
    ..Finally, both C-terminal Cys residues are palmitoylated, and dual acylation is required for efficient membrane association. ..
  7. Yinan M, Yu Q, Zhiyue C, Jianjun L, Lie H, Liping Z, et al. Polymorphisms of casein kinase I gamma 2 gene associated with simple febrile seizures in Chinese Han population. Neurosci Lett. 2004;368:2-6 pubmed
    b>Casein kinase I gamma 2 isoform (CSNK1G2), a member of the large casein kinase I (CKI) family, may affect the development of brain, and associate with vesicular trafficking and neurotransmitter releasing from small synaptic vesicles...
  8. Papanayotou I, Sun B, Roth A, Davis N. Protein aggregation induced during glass bead lysis of yeast. Yeast. 2010;27:801-16 pubmed publisher
  9. Shanware N, Hutchinson J, Kim S, Zhan L, Bowler M, Tibbetts R. Casein kinase 1-dependent phosphorylation of familial advanced sleep phase syndrome-associated residues controls PERIOD 2 stability. J Biol Chem. 2011;286:12766-74 pubmed publisher
    ..Our combined findings provide new insights into PER2 regulation and the biochemical basis of FASPS. ..

More Information


  1. Reinhardt J, Ferandin Y, Meijer L. Purification of CK1 by affinity chromatography on immobilised axin. Protein Expr Purif. 2007;54:101-9 pubmed
  2. Inuzuka H, Tseng A, Gao D, Zhai B, Zhang Q, Shaik S, et al. Phosphorylation by casein kinase I promotes the turnover of the Mdm2 oncoprotein via the SCF(beta-TRCP) ubiquitin ligase. Cancer Cell. 2010;18:147-59 pubmed publisher
    ..Here, we report that Mdm2 is rapidly degraded after DNA damage and that phosphorylation of Mdm2 by casein kinase I (CKI) at multiple sites triggers its interaction with, and subsequent ubiquitination and destruction, by SCF(..
  3. Jia J, Tong C, Wang B, Luo L, Jiang J. Hedgehog signalling activity of Smoothened requires phosphorylation by protein kinase A and casein kinase I. Nature. 2004;432:1045-50 pubmed
    ..Here we show that protein kinase A (PKA) and casein kinase I (CKI) regulate Smo cell-surface accumulation and activity in response to Hh...
  4. Hickey C, Stroupe C, Wickner W. The major role of the Rab Ypt7p in vacuole fusion is supporting HOPS membrane association. J Biol Chem. 2009;284:16118-25 pubmed publisher
    ..Thus, although Ypt7p may contribute to other fusion functions, its central role is to bind HOPS to the membrane. ..
  5. Ishiguro T, Tanaka K, Sakuno T, Watanabe Y. Shugoshin-PP2A counteracts casein-kinase-1-dependent cleavage of Rec8 by separase. Nat Cell Biol. 2010;12:500-6 pubmed publisher
    ..Thus, our studies prove the key notion that the balance between Rec8 phosphorylation and its dephosphorylation by Sgo1-PP2A regulates the step-wise loss of chromosomal cohesion in meiosis...
  6. Ray P, Basu U, Ray A, Majumdar R, Deng H, Maitra U. The Saccharomyces cerevisiae 60 S ribosome biogenesis factor Tif6p is regulated by Hrr25p-mediated phosphorylation. J Biol Chem. 2008;283:9681-91 pubmed publisher
    ..the present work, using molecular genetic and biochemical analyses, we show that Hrr25p, an isoform of yeast casein kinase I, phosphorylates Tif6p both in vitro and in vivo...
  7. Albornoz A, Yáñez J, Foerster C, Aguirre C, Pereiro L, Burzio V, et al. The CK1 gene family: expression patterning in zebrafish development. Biol Res. 2007;40:251-66 pubmed
    ..This is the first time that a detailed comparison of the expression of CK1 family genes is directly assessed in a vertebrate system throughout development. ..
  8. Cabrera M, Langemeyer L, Mari M, Rethmeier R, Orban I, Perz A, et al. Phosphorylation of a membrane curvature-sensing motif switches function of the HOPS subunit Vps41 in membrane tethering. J Cell Biol. 2010;191:845-59 pubmed publisher
    ..This multifunctional tethering factor thus discriminates between trafficking routes by switching from a curvature-sensing to a coat recognition mode upon phosphorylation. ..
  9. LaGrassa T, Ungermann C. The vacuolar kinase Yck3 maintains organelle fragmentation by regulating the HOPS tethering complex. J Cell Biol. 2005;168:401-14 pubmed
    ..We report here that maintenance of the fragmented phenotype requires the vacuolar casein kinase I Yck3: when Yck3 is absent, salt-stressed vacuoles undergo fission, but reassemble in a SNARE-dependent manner,..
  10. Robinson L, Hubbard E, Graves P, DePaoli Roach A, Roach P, Kung C, et al. Yeast casein kinase I homologues: an essential gene pair. Proc Natl Acad Sci U S A. 1992;89:28-32 pubmed
    ..Partial sequence obtained for rabbit casein kinase I shares 64% identity with the two yeast gene products...
  11. Omnus D, Ljungdahl P. Rts1-protein phosphatase 2A antagonizes Ptr3-mediated activation of the signaling protease Ssy5 by casein kinase I. Mol Biol Cell. 2013;24:1480-92 pubmed publisher
    ..Activation of the processing protease Ssy5 depends on the signal-induced phosphorylation of its prodomain by casein kinase I (Yck1/2)...
  12. Wang X, Hoekstra M, DeMaggio A, Dhillon N, Vancura A, Kuret J, et al. Prenylated isoforms of yeast casein kinase I, including the novel Yck3p, suppress the gcs1 blockage of cell proliferation from stationary phase. Mol Cell Biol. 1996;16:5375-85 pubmed
    ..Among these are YCK1 (CK12) and YCK2 (CKI1), encoding membrane-associated casein kinase I, and YCK3, encoding a novel casein kinase I isoform...
  13. Robinson L, Bradley C, Bryan J, Jerome A, Kweon Y, Panek H. The Yck2 yeast casein kinase 1 isoform shows cell cycle-specific localization to sites of polarized growth and is required for proper septin organization. Mol Biol Cell. 1999;10:1077-92 pubmed
    ..The sites of GFP-Yck2p concentration and the defects observed for Yck-deficient cells together suggest that Yck plays distinct roles in morphogenesis and cytokinesis that are effected by differential localization. ..
  14. Yamamoto A, Friedlein A, Imai Y, Takahashi R, Kahle P, Haass C. Parkin phosphorylation and modulation of its E3 ubiquitin ligase activity. J Biol Chem. 2005;280:3390-9 pubmed
    ..Thus, complex regulation of the phosphorylation state of parkin may contribute to the unfolded protein response in stressed cells. ..
  15. MacLaine N, Oster B, Bundgaard B, Fraser J, Buckner C, Lazo P, et al. A central role for CK1 in catalyzing phosphorylation of the p53 transactivation domain at serine 20 after HHV-6B viral infection. J Biol Chem. 2008;283:28563-73 pubmed publisher
  16. Davidson G, Wu W, Shen J, Bilic J, Fenger U, Stannek P, et al. Casein kinase 1 gamma couples Wnt receptor activation to cytoplasmic signal transduction. Nature. 2005;438:867-72 pubmed publisher
    ..Our results reveal an evolutionarily conserved mechanism that couples Wnt receptor activation to the cytoplasmic signal transduction apparatus...
  17. Gokhale A, Wirschell M, Sale W. Regulation of dynein-driven microtubule sliding by the axonemal protein kinase CK1 in Chlamydomonas flagella. J Cell Biol. 2009;186:817-24 pubmed publisher
    Experimental analysis of isolated ciliary/flagellar axonemes has implicated the protein kinase casein kinase I (CK1) in regulation of dynein...
  18. Kim M, Go Y, Lee S, Kim Y, Shin J, Min M, et al. Seed-expressed casein kinase I acts as a positive regulator of the SeFAD2 promoter via phosphorylation of the SebHLH transcription factor. Plant Mol Biol. 2010;73:425-37 pubmed publisher
    ..shares approximately 80% sequence identity with other putative casein kinases and was named SeCKI (Sesame Casein Kinase I)...
  19. Anand V, Daboussi L, Lorenz T, Payne G. Genome-wide analysis of AP-3-dependent protein transport in yeast. Mol Biol Cell. 2009;20:1592-604 pubmed publisher
    ..We propose that the cargo-selective nature of the AP-3 pathway in yeast is achieved by AP-3 and Yck3p functioning in concert with machinery shared by other vacuolar transport pathways. ..
  20. Lord C, Bhandari D, Menon S, Ghassemian M, Nycz D, HAY J, et al. Sequential interactions with Sec23 control the direction of vesicle traffic. Nature. 2011;473:181-6 pubmed publisher
    ..These events are conserved in mammalian cells. ..
  21. Dupre Crochet S, Figueroa A, Hogan C, Ferber E, Bialucha C, Adams J, et al. Casein kinase 1 is a novel negative regulator of E-cadherin-based cell-cell contacts. Mol Cell Biol. 2007;27:3804-16 pubmed
    ..These data indicate that CK1 is a novel negative regulator of cadherin-based cell-cell contacts. ..
  22. Takeda K, Cabrera M, Rohde J, Bausch D, Jensen O, Ungermann C. The vacuolar V1/V0-ATPase is involved in the release of the HOPS subunit Vps41 from vacuoles, vacuole fragmentation and fusion. FEBS Lett. 2008;582:1558-63 pubmed publisher
    ..Our data suggest a connection between vacuole biogenesis and membrane fusion. ..
  23. Sun B, Chen L, Cao W, Roth A, Davis N. The yeast casein kinase Yck3p is palmitoylated, then sorted to the vacuolar membrane with AP-3-dependent recognition of a YXXPhi adaptin sorting signal. Mol Biol Cell. 2004;15:1397-406 pubmed
    ..Although YXXPhi signals have a well-appreciated role in the adaptin-mediated sorting of mammalian cells, this is the first signal of this class to be identified in yeast. ..
  24. Smelkinson M, Zhou Q, Kalderon D. Regulation of Ci-SCFSlimb binding, Ci proteolysis, and hedgehog pathway activity by Ci phosphorylation. Dev Cell. 2007;13:481-95 pubmed
    ..We also show that when Ci proteolysis is compromised, its specific activity is limited principally by Su(fu), and not by Cos2 cytoplasmic tethering or PKA phosphorylation. ..
  25. Verkaar F, van der Doelen A, Smits J, Blankesteijn W, Zaman G. Inhibition of Wnt/?-catenin signaling by p38 MAP kinase inhibitors is explained by cross-reactivity with casein kinase I?/?. Chem Biol. 2011;18:485-94 pubmed publisher
    ..Profiling of TAK-715 and AMG-548 against a panel of over 200 kinases revealed cross-reactivity with casein kinase I? and ?, which are known activators of Wnt/?-catenin signaling...
  26. Abdel Sater F, El Bakkoury M, Urrestarazu A, Vissers S, Andre B. Amino acid signaling in yeast: casein kinase I and the Ssy5 endoprotease are key determinants of endoproteolytic activation of the membrane-bound Stp1 transcription factor. Mol Cell Biol. 2004;24:9771-85 pubmed
    ..Here we show that Stp1 undergoes casein kinase I-dependent phosphorylation...
  27. Abdel Sater F, Jean C, Merhi A, Vissers S, Andre B. Amino acid signaling in yeast: activation of Ssy5 protease is associated with its phosphorylation-induced ubiquitylation. J Biol Chem. 2011;286:12006-15 pubmed publisher
    ..We here report that the prodomain of Ssy5 is phosphorylated in a casein kinase I-dependent manner in response to amino acid detection...
  28. Flajolet M, He G, Heiman M, Lin A, Nairn A, Greengard P. Regulation of Alzheimer's disease amyloid-beta formation by casein kinase I. Proc Natl Acad Sci U S A. 2007;104:4159-64 pubmed
    ..Importantly, Notch cleavage was not affected. Our results indicate that CK1 represents a therapeutic target for prevention of Abeta formation in AD. ..
  29. Tan Y, Yu D, Pletting J, Davis R. Gilgamesh is required for rutabaga-independent olfactory learning in Drosophila. Neuron. 2010;67:810-20 pubmed publisher
    ..From a screen for new memory mutants, we identified alleles of the gilgamesh (gish) gene, which encodes a casein kinase I? homolog that is preferentially expressed in the mushroom body neurons...
  30. Hori K, Ogiso Tanaka E, Matsubara K, Yamanouchi U, Ebana K, Yano M. Hd16, a gene for casein kinase I, is involved in the control of rice flowering time by modulating the day-length response. Plant J. 2013;76:36-46 pubmed publisher
    ..These results demonstrate that Hd16 acts as an inhibitor in the rice flowering pathway by enhancing the photoperiod response as a result of the phosphorylation of Ghd7...
  31. Cheong J, Virshup D. Casein kinase 1: Complexity in the family. Int J Biochem Cell Biol. 2011;43:465-9 pubmed publisher
    ..We provide a brief overview of the fundamentals of CK1 biology with an emphasis on scaffold binding and kinase regulation in Wnt signaling and circadian rhythms. ..
  32. Hou H, John Peter A, Meiringer C, Subramanian K, Ungermann C. Analysis of DHHC acyltransferases implies overlapping substrate specificity and a two-step reaction mechanism. Traffic. 2009;10:1061-73 pubmed publisher
    ..Thus, the intracellular distribution of DHHC proteins provides an acyltransferase network, which may promote dynamic membrane association of substrate proteins. ..
  33. Hoekstra M, Liskay R, Ou A, DeMaggio A, Burbee D, Heffron F. HRR25, a putative protein kinase from budding yeast: association with repair of damaged DNA. Science. 1991;253:1031-4 pubmed
    ..Taken together, the hrr25 mutant phenotypes and the features of the gene product indicate that HRR25 is a distinctive member of the protein kinase superfamily. ..
  34. Nerusheva O, Dorogova N, Gubanova N, Yudina O, Omelyanchuk L. A GFP trap study uncovers the functions of Gilgamesh protein kinase in Drosophila melanogaster spermatogenesis. Cell Biol Int. 2009;33:586-93 pubmed publisher
    ..Ultrastructural evidence confirmed defective spermatid individualization due to the mutation. The phylogenetic origin of the protein, and the connection between vesicular trafficking and spermatid individualization, are discussed. ..
  35. Grozav A, Chikamori K, Kozuki T, Grabowski D, Bukowski R, Willard B, et al. Casein kinase I delta/epsilon phosphorylates topoisomerase IIalpha at serine-1106 and modulates DNA cleavage activity. Nucleic Acids Res. 2009;37:382-92 pubmed publisher
    ..These results provide strong support for an essential role of CKIdelta/epsilon in phosphorylating Ser-1106 in human topo IIalpha and in regulating enzyme function. ..
  36. Pasula S, Jouandot D, Kim J. Biochemical evidence for glucose-independent induction of HXT expression in Saccharomyces cerevisiae. FEBS Lett. 2007;581:3230-4 pubmed
    ..Finally, we show that active Snf1 protein kinase in high glucose prevents degradation of Mth1 and Std1. ..
  37. Urbaniak M. Casein kinase 1 isoform 2 is essential for bloodstream form Trypanosoma brucei. Mol Biochem Parasitol. 2009;166:183-5 pubmed publisher
    ..These data show that TbCK1.2 is an attractive target for anti-trypanosomal drug discovery...
  38. Gadura N, Robinson L, Michels C. Glc7-Reg1 phosphatase signals to Yck1,2 casein kinase 1 to regulate transport activity and glucose-induced inactivation of Saccharomyces maltose permease. Genetics. 2006;172:1427-39 pubmed
  39. Rena G, Bain J, Elliott M, Cohen P. D4476, a cell-permeant inhibitor of CK1, suppresses the site-specific phosphorylation and nuclear exclusion of FOXO1a. EMBO Rep. 2004;5:60-5 pubmed
    ..D4476 is much more potent and specific than IC261 or CKI-7, and is therefore the most useful CK1 inhibitor currently available for identifying physiological substrates of CK1. ..
  40. Wang B, Li Y. Evidence for the direct involvement of {beta}TrCP in Gli3 protein processing. Proc Natl Acad Sci U S A. 2006;103:33-8 pubmed
    ..Our findings provide evidence for a direct link between phosphorylation of Gli3/Ci proteins and betaTrCP/Slimb action, thus supporting the hypothesis that the processing of Gli3/Ci is affected by the proteasome. ..
  41. Zhai L, Graves P, Robinson L, Italiano M, Culbertson M, Rowles J, et al. Casein kinase I gamma subfamily. Molecular cloning, expression, and characterization of three mammalian isoforms and complementation of defects in the Saccharomyces cerevisiae YCK genes. J Biol Chem. 1995;270:12717-24 pubmed
    b>Casein kinase I, one of the first protein kinases identified biochemically, is known to exist in multiple isoforms in mammals...
  42. Foucher A, Rachidi N, Gharbi S, Blisnick T, Bastin P, Pemberton I, et al. Apoptotic marker expression in the absence of cell death in staurosporine-treated Leishmania donovani. Antimicrob Agents Chemother. 2013;57:1252-61 pubmed publisher
  43. Robinson L, Menold M, Garrett S, Culbertson M. Casein kinase I-like protein kinases encoded by YCK1 and YCK2 are required for yeast morphogenesis. Mol Cell Biol. 1993;13:2870-81 pubmed
    b>Casein kinase I is an acidotropic protein kinase class that is widely distributed among eukaryotic cell types...
  44. Omnus D, Pfirrmann T, Andréasson C, Ljungdahl P. A phosphodegron controls nutrient-induced proteasomal activation of the signaling protease Ssy5. Mol Biol Cell. 2011;22:2754-65 pubmed publisher
    ..change triggers phosphodegron phosphorylation by the constitutively active plasma membrane-localized casein kinase I (Yck1/2)...
  45. Estrada E, Agostinis P, Vandenheede J, Goris J, Merlevede W, Francois J, et al. Phosphorylation of yeast plasma membrane H+-ATPase by casein kinase I. J Biol Chem. 1996;271:32064-72 pubmed
    The plasma membrane H+-ATPase of Saccharomyces cerevisiae is subject to phosphorylation by a casein kinase I activity in vitro...
  46. Izeradjene K, Douglas L, Delaney A, Houghton J. Casein kinase I attenuates tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by regulating the recruitment of fas-associated death domain and procaspase-8 to the death-inducing signaling complex. Cancer Res. 2004;64:8036-44 pubmed
    ..We have demonstrated that casein kinase I can attenuate TRAIL-induced apoptosis in human cell lines derived from colon adenocarcinoma (HT29 and HCT8) ..
  47. Apionishev S, Katanayeva N, Marks S, Kalderon D, Tomlinson A. Drosophila Smoothened phosphorylation sites essential for Hedgehog signal transduction. Nat Cell Biol. 2005;7:86-92 pubmed
  48. Smelkinson M, Kalderon D. Processing of the Drosophila hedgehog signaling effector Ci-155 to the repressor Ci-75 is mediated by direct binding to the SCF component Slimb. Curr Biol. 2006;16:110-6 pubmed
    ..We also explore the phosphorylated motifs in Ci that are recognized by Slimb and provide some evidence that silencing of Ci-155 by phosphorylation may involve more than binding to Slimb. ..
  49. Schäfer T, Maco B, Petfalski E, Tollervey D, Bottcher B, Aebi U, et al. Hrr25-dependent phosphorylation state regulates organization of the pre-40S subunit. Nature. 2006;441:651-5 pubmed
    ..In vivo depletion of Hrr25 inhibits growth and leads to the accumulation of immature 40S subunits that contain unstably bound Rps3. We conclude that the kinase activity of Hrr25 regulates the maturation of 40S ribosomal subunits. ..
  50. Kametani F, Nonaka T, Suzuki T, Arai T, Dohmae N, Akiyama H, et al. Identification of casein kinase-1 phosphorylation sites on TDP-43. Biochem Biophys Res Commun. 2009;382:405-9 pubmed publisher
    ..Interestingly, 18 of them were located in the C-terminal glycine-rich region of TDP-43. Our results indicate that CK1-mediated phosphorylation may play a role in the pathogenesis of these diseases. ..
  51. Shanware N, Williams L, Bowler M, Tibbetts R. Non-specific in vivo inhibition of CK1 by the pyridinyl imidazole p38 inhibitors SB 203580 and SB 202190. BMB Rep. 2009;42:142-7 pubmed
  52. Price M. CKI, there's more than one: casein kinase I family members in Wnt and Hedgehog signaling. Genes Dev. 2006;20:399-410 pubmed
    Multiple members of the casein kinase I family of serine/threonine protein kinases are involved in positive and negative roles in Wnt and Hedgehog signaling...
  53. Cabrera M, Ostrowicz C, Mari M, LaGrassa T, Reggiori F, Ungermann C. Vps41 phosphorylation and the Rab Ypt7 control the targeting of the HOPS complex to endosome-vacuole fusion sites. Mol Biol Cell. 2009;20:1937-48 pubmed publisher
    ..Our data suggest that Vps41 phosphorylation fine-tunes the organization of vacuole fusion sites and provide evidence for a fusion "hot spot" on the vacuole limiting membrane. ..