Gene Symbol: CkIalpha
Description: Casein kinase Ialpha
Alias: CG2028, CK I, CK1, CK1a, CK1alpha, CKI, CKI alpha, CKIa, CKIalpha, Ck1alpha, CkI alpha, CkIa, Dmel\CG2028, PKA-C, anon-WO03040301.93, anon-WO03040301.95, ck1a, ck1alpha, dmCK1, dmckI, l(1)G0492, casein kinase ialpha, CG2028-PA, CG2028-PB, CG2028-PD, CG2028-PE, CG2028-PF, CG2028-PG, CkIalpha-PA, CkIalpha-PB, CkIalpha-PD, CkIalpha-PE, CkIalpha-PF, CkIalpha-PG, caesin kinase I alpha, casein kinase 1, casein kinase 1a, casein kinase 1alpha, casein kinase I, casein kinase-1
Species: fruit fly

Top Publications

  1. Yanagawa S, Matsuda Y, Lee J, Matsubayashi H, Sese S, Kadowaki T, et al. Casein kinase I phosphorylates the Armadillo protein and induces its degradation in Drosophila. EMBO J. 2002;21:1733-42 pubmed
    b>Casein kinase I (CKI) was recently reported as a positive regulator of Wnt signaling in vertebrates and Caenorhabditis elegans...
  2. Liu C, Li Y, Semenov M, Han C, Baeg G, Tan Y, et al. Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell. 2002;108:837-47 pubmed
    ..This "priming" kinase is casein kinase Ialpha (CKIalpha)...
  3. 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
    ..This processing requires phosphorylation of full-length Ci (Ci-155) by protein kinase A (PKA), casein kinase 1 (CK1), and glycogen synthase kinase 3 (GSK3), as well as the activity of Slimb ...
  4. Santos J, Logarinho E, Tapia C, Allende C, Allende J, Sunkel C. The casein kinase 1 alpha gene of Drosophila melanogaster is developmentally regulated and the kinase activity of the protein induced by DNA damage. J Cell Sci. 1996;109 ( Pt 7):1847-56 pubmed the molecular cloning and characterisation of the first CK1(casein kinase) gene of Drosophila melanogaster (dmCK1)...
  5. 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...
  6. Mennella V, Tan D, Buster D, Asenjo A, Rath U, Ma A, et al. Motor domain phosphorylation and regulation of the Drosophila kinesin 13, KLP10A. J Cell Biol. 2009;186:481-90 pubmed publisher
    ..Finally, we identify casein kinase 1alpha as a possible candidate for KLP10A phosphorylation...
  7. Jia J, Zhang L, Zhang Q, Tong C, Wang B, Hou F, et al. Phosphorylation by double-time/CKIepsilon and CKIalpha targets cubitus interruptus for Slimb/beta-TRCP-mediated proteolytic processing. Dev Cell. 2005;9:819-30 pubmed
    ..Ci processing requires sequential phosphorylation by PKA, GSK3, and a casein kinase I (CKI) family member(s)...
  8. Spratford C, Kumar J. Extramacrochaetae imposes order on the Drosophila eye by refining the activity of the Hedgehog signaling gradient. Development. 2013;140:1994-2004 pubmed publisher
    ..Secondary furrow initiation along the dorsal and ventral margins is blocked by the activity of the Wingless (Wg) pathway. We also show that Emc regulates and cooperates with Wg signaling to inhibit lateral furrow initiation. ..
  9. Cadigan K. Wnt signaling--20 years and counting. Trends Genet. 2002;18:340-2 pubmed

More Information


  1. Preuss F, Fan J, Kalive M, Bao S, Schuenemann E, Bjes E, et al. Drosophila doubletime mutations which either shorten or lengthen the period of circadian rhythms decrease the protein kinase activity of casein kinase I. Mol Cell Biol. 2004;24:886-98 pubmed
    In both mammals and fruit flies, casein kinase I has been shown to regulate the circadian phosphorylation of the period protein (PER)...
  2. Galletti M, Riccardo S, Parisi F, Lora C, Saqcena M, Rivas L, et al. Identification of domains responsible for ubiquitin-dependent degradation of dMyc by glycogen synthase kinase 3beta and casein kinase 1 kinases. Mol Cell Biol. 2009;29:3424-34 pubmed publisher
    ..Drosophila homologue of the human c-myc proto-oncogene, is regulated in vitro and in vivo by members of the casein kinase 1 (CK1) family and by glycogen synthase kinase 3beta (GSK3beta)...
  3. Tolwinski N. New advances in signaling and pattern formation. Fly (Austin). 2007;1:116-7 pubmed
  4. Bienz M, Hamada F. Adenomatous polyposis coli proteins and cell adhesion. Curr Opin Cell Biol. 2004;16:528-35 pubmed
    ..Thus, APC--like beta-catenin/Armadillo--may have a dual role in Wnt signal transduction and in cellular adhesion, which could be relevant to its activity as a tumour suppressor. ..
  5. 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
    ..Together, Protein Kinase A, Casein Kinase 1 and Glycogen Synthase Kinase 3 silence the pathway in the absence of ligand by phosphorylating Ci at a ..
  6. Kalderon D. Hedgehog signaling: an Arrestin connection?. Curr Biol. 2005;15:R175-8 pubmed
    ..New binding, localization and genetic studies suggest that Arrestins may also participate in the transduction of Hedgehog signals by the seven transmembrane domain protein, Smoothened. ..
  7. Buechling T, Bartscherer K, Ohkawara B, Chaudhary V, Spirohn K, Niehrs C, et al. Wnt/Frizzled signaling requires dPRR, the Drosophila homolog of the prorenin receptor. Curr Biol. 2010;20:1263-8 pubmed publisher
    ..Furthermore, dPRR binds to Fz and Fz2 receptors. In summary, our data suggest that dPRR has an evolutionarily conserved role at the receptor level for activation of canonical and noncanonical Wnt/Fz signaling pathways...
  8. Matsubayashi H, Sese S, Lee J, Shirakawa T, Iwatsubo T, Tomita T, et al. Biochemical characterization of the Drosophila wingless signaling pathway based on RNA interference. Mol Cell Biol. 2004;24:2012-24 pubmed
    ..Zw3)-mediated Arm phosphorylation has been implicated in its degradation, we have recently shown that casein kinase Ialpha (CKIalpha) also phosphorylates Arm and induces its degradation...
  9. D Ambrosio M, Vale R. A whole genome RNAi screen of Drosophila S2 cell spreading performed using automated computational image analysis. J Cell Biol. 2010;191:471-8 pubmed publisher
    ..Expected genes in the Scar-Arp2/3 actin nucleation pathway were identified as well as casein kinase I, which had a similar morphological RNAi signature...
  10. Fearon E, Cadigan K. Cell biology. Wnt signaling glows with RNAi. Science. 2005;308:801-3 pubmed
  11. Bulat V, Rast M, Pielage J. Presynaptic CK2 promotes synapse organization and stability by targeting Ankyrin2. J Cell Biol. 2014;204:77-94 pubmed publisher
    ..Our study identifies phosphorylation of structural synaptic components as a compelling mechanism to actively control the development and longevity of synaptic connections. ..
  12. Lefers M, Holmgren R. Ci proteolysis: regulation by a constellation of phosphorylation sites. Curr Biol. 2002;12:R422-3 pubmed
    Proteolytic processing of Ci requires phosphorylation by the kinases Sgg/GSK3 and CK1. The newly identified phosphorylation sites form clusters with previously described PKA sites in which phosphorylation by PKA acts to prime subsequent ..
  13. 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...
  14. Seto E, Bellen H. Internalization is required for proper Wingless signaling in Drosophila melanogaster. J Cell Biol. 2006;173:95-106 pubmed
    ..As these data indicate that endosomal transport promotes Wg signaling, our findings suggest that the regulation of endocytosis is a novel mechanism through which Wg signaling levels are determined. ..
  15. Takada R, Hijikata H, Kondoh H, Takada S. Analysis of combinatorial effects of Wnts and Frizzleds on beta-catenin/armadillo stabilization and Dishevelled phosphorylation. Genes Cells. 2005;10:919-28 pubmed
    ..This Dsh phosphorylation is abrogated by decreasing the levels of casein kinase I alpha by double-stranded RNA-mediated translational interference...
  16. Jia H, Liu Y, Yan W, Jia J. PP4 and PP2A regulate Hedgehog signaling by controlling Smo and Ci phosphorylation. Development. 2009;136:307-16 pubmed publisher
    ..Taken together, our results suggest that PP4 and PP2A are two phosphatases that act at different positions of the Hh signaling cascade. ..
  17. 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
    ..Here we show that multiple successively phosphorylated CK1 sites on Ci create an atypical extended binding site for the SCF substrate recognition component Slimb...
  18. Liu Y, Cao X, Jiang J, Jia J. Fused-Costal2 protein complex regulates Hedgehog-induced Smo phosphorylation and cell-surface accumulation. Genes Dev. 2007;21:1949-63 pubmed
    ..Our data suggest that Cos2-Smo interaction blocks Hh-induced Smo phosphorylation, and that Fu promotes Smo phosphorylation by antagonizing Cos2. ..
  19. Zhang W, Zhao Y, Tong C, Wang G, Wang B, Jia J, et al. Hedgehog-regulated Costal2-kinase complexes control phosphorylation and proteolytic processing of Cubitus interruptus. Dev Cell. 2005;8:267-78 pubmed
    ..In Drosophila, Hh counteracts phosphorylation by PKA, GSK3, and CKI to prevent Cubitus interruptus (Ci) processing through unknown mechanisms...
  20. Ishii S. Costal-2: a scaffold for kinases mediates Hedgehog signaling. Dev Cell. 2005;8:140-1 pubmed
    ..In this issue of Developmental Cell, a report by Zhang et al. provides evidence that the kinesin-related protein Costal-2 forms a multi-component scaffold that mediates Hedgehog signaling. ..
  21. Collu G, Hidalgo Sastre A, Brennan K. Wnt-Notch signalling crosstalk in development and disease. Cell Mol Life Sci. 2014;71:3553-67 pubmed publisher
    ..In this review, we will outline the two signalling pathways, describe the different points of interaction between them, and cover how these interactions influence development and disease. ..
  22. Strutt H, Price M, Strutt D. Planar polarity is positively regulated by casein kinase Iepsilon in Drosophila. Curr Biol. 2006;16:1329-36 pubmed
    Members of the casein kinase I (CKI) family have been implicated in regulating canonical Wnt/Wingless (Wg) signaling by phosphorylating multiple pathway components...
  23. Kim K, Vinayagam A, Perrimon N. A rapid genome-wide microRNA screen identifies miR-14 as a modulator of Hedgehog signaling. Cell Rep. 2014;7:2066-77 pubmed publisher
    ..Altogether, our systematic screening platform is a powerful approach to identifying both physiological and apparent nonphysiological targets of miRNAs, which are relevant in both normal and diseased tissues. ..
  24. Feng Y, Irvine K. Processing and phosphorylation of the Fat receptor. Proc Natl Acad Sci U S A. 2009;106:11989-94 pubmed publisher
  25. Zhang C, Williams E, Guo Y, Lum L, Beachy P. Extensive phosphorylation of Smoothened in Hedgehog pathway activation. Proc Natl Acad Sci U S A. 2004;101:17900-7 pubmed
    ..Our studies confirm and extend previous studies showing a positive effect for cAMP-dependent protein kinase and uncover a positive role for casein kinase 1alpha in Hh pathway activation.
  26. Behrens J. Cross-regulation of the Wnt signalling pathway: a role of MAP kinases. J Cell Sci. 2000;113 ( Pt 6):911-9 pubmed
    ..Since TAK1 is activated by TGF-(beta) and various cytokines, it might provide an entry point for regulation of the Wnt system by other pathways. In addition, alterations in TAK1-NLK might play a role in cancer. ..
  27. Zhao Y, Tong C, Jiang J. Transducing the Hedgehog signal across the plasma membrane. Fly (Austin). 2007;1:333-6 pubmed
    ..In Drosophila, Hh induces phosphorylation of Smo at multiple sites by PKA and CK1, leading to its cell surface accumulation and activation...
  28. Nawathean P, Rosbash M. The doubletime and CKII kinases collaborate to potentiate Drosophila PER transcriptional repressor activity. Mol Cell. 2004;13:213-23 pubmed
    ..This interpretation suggests further that the circadian regulation of PER nuclear localization in flies reflects changes in PER transcriptional activity rather than in PER nuclear import or export activity. ..
  29. Kalderon D. Similarities between the Hedgehog and Wnt signaling pathways. Trends Cell Biol. 2002;12:523-31 pubmed
    ..Recently, the common use of glycogen synthase kinase 3 and casein kinase 1 has been added to a growing list of straightforward similarities between Hedgehog and Wnt signaling pathways...
  30. Jiang J. Degrading Ci: who is Cul-pable?. Genes Dev. 2002;16:2315-21 pubmed
  31. Komori H, Xiao Q, McCartney B, Lee C. Brain tumor specifies intermediate progenitor cell identity by attenuating ?-catenin/Armadillo activity. Development. 2014;141:51-62 pubmed publisher
    ..Thus, the Brat-dependent mechanism extinguishes the function of the self-renewal factor Klu in the presumptive intermediate progenitor cell by attenuating Arm activity, balancing stem cell maintenance and progenitor cell specification. ..
  32. Li S, Li S, Han Y, Tong C, Wang B, Chen Y, et al. Regulation of Smoothened Phosphorylation and High-Level Hedgehog Signaling Activity by a Plasma Membrane Associated Kinase. PLoS Biol. 2016;14:e1002481 pubmed publisher
    ..Here we show that Hh stimulates the binding of Smo to a plasma membrane-associated kinase Gilgamesh (Gish)/CK1? and that Gish fine-tunes Hh pathway activity by phosphorylating a Ser/Thr cluster (CL-II) in the juxtamembrane ..
  33. Xiong Y, Liu C, Zhao Y. Decoding Ci: from partial degradation to inhibition. Dev Growth Differ. 2015;57:98-108 pubmed publisher
    ..Overall, we intend to offer an overview on how Ci responds to and relays Hh signals in a precise manner to control target genes expressions and ensures proper Hh signal transduction. ..
  34. Hartl T, Scott M. Wing tips: The wing disc as a platform for studying Hedgehog signaling. Methods. 2014;68:199-206 pubmed publisher
    ..The tools and approaches we highlight form the cornerstone of research efforts in many laboratories that use Drosophila to study Hh signaling, and are essential for ongoing discoveries. ..
  35. Furlong E. A functional genomics approach to identify new regulators of Wnt signaling. Dev Cell. 2005;8:624-6 pubmed
    ..Supporting in vivo studies are in progress. The fact that such an impressive number of potential modulators had eluded detection in genetic screens underscores the potential of applying new, high-throughput approaches to old problems. ..
  36. Sekine T, Yamaguchi T, Hamano K, Young M, Shimoda M, Saez L. Casein kinase I epsilon does not rescue double-time function in Drosophila despite evolutionarily conserved roles in the circadian clock. J Biol Rhythms. 2008;23:3-15 pubmed publisher
    ..Genetic and biochemical studies have shown that dbt and its mammalian ortholog casein kinase I epsilon (hckI epsilon) regulate the circadian phosphorylation of period (per), thus controlling per ..
  37. Lum L, Beachy P. The Hedgehog response network: sensors, switches, and routers. Science. 2004;304:1755-9 pubmed
  38. Kanao T, Sawada T, Davies S, Ichinose H, Hasegawa K, Takahashi R, et al. The nitric oxide-cyclic GMP pathway regulates FoxO and alters dopaminergic neuron survival in Drosophila. PLoS ONE. 2012;7:e30958 pubmed publisher
    ..These results strongly suggest that the NO-FoxO axis contributes to DA neurodegeneration in LRRK2-linked PD. ..
  39. Buechling T, Chaudhary V, Spirohn K, Weiss M, Boutros M. p24 proteins are required for secretion of Wnt ligands. EMBO Rep. 2011;12:1265-72 pubmed publisher
    ..Our results indicate that Wnt secretion relies on a specialized anterograde secretion route with p24 proteins functioning as conserved cargo receptors. ..
  40. Voolstra O, Bartels J, Oberegelsbacher C, Pfannstiel J, Huber A. Phosphorylation of the Drosophila transient receptor potential ion channel is regulated by the phototransduction cascade and involves several protein kinases and phosphatases. PLoS ONE. 2013;8:e73787 pubmed publisher
    ..A candidate screen to identify kinases and phosphatases provided in vivo evidence for an involvement of eye-PKC as well as other kinases and phosphatases in TRP phosphorylation. ..
  41. Shi Q, Li S, Jia J, Jiang J. The Hedgehog-induced Smoothened conformational switch assembles a signaling complex that activates Fused by promoting its dimerization and phosphorylation. Development. 2011;138:4219-31 pubmed publisher
  42. Zhou Q, Kalderon D. Hedgehog activates fused through phosphorylation to elicit a full spectrum of pathway responses. Dev Cell. 2011;20:802-14 pubmed publisher
    ..Here we show that the Fused (Fu) protein kinase is activated by Smo and Cos2 via Fu- and CK1-dependent phosphorylation...
  43. Swarup S, Verheyen E. Drosophila homeodomain-interacting protein kinase inhibits the Skp1-Cul1-F-box E3 ligase complex to dually promote Wingless and Hedgehog signaling. Proc Natl Acad Sci U S A. 2011;108:9887-92 pubmed publisher
    ..Thus, similar to casein kinase 1 and glycogen synthase kinase 3, Hipk dually regulates both Wingless and Hedgehog signaling by controlling the ..
  44. Shi Q, Li S, Li S, Jiang A, Chen Y, Jiang J. Hedgehog-induced phosphorylation by CK1 sustains the activity of Ci/Gli activator. Proc Natl Acad Sci U S A. 2014;111:E5651-60 pubmed publisher
    ..Here we demonstrate that Casein kinase 1 (CK1) sustains Hh signaling downstream of Costal2 and Suppressor of fused (Sufu) by protecting Ci(A) from ..
  45. Nguyen H, Nye J, Buster D, Klebba J, Rogers G, Bosco G. Drosophila casein kinase I alpha regulates homolog pairing and genome organization by modulating condensin II subunit Cap-H2 levels. PLoS Genet. 2015;11:e1005014 pubmed publisher
    ..Here, we identify Casein Kinase I alpha (CK1α) as an additional negative-regulator of Cap-H2...
  46. Zhang L, Jia J, Wang B, Amanai K, Wharton K, Jiang J. Regulation of wingless signaling by the CKI family in Drosophila limb development. Dev Biol. 2006;299:221-37 pubmed
    ..Recent studies suggest that casein kinase I (CKI) family members play pivotal roles in the Wg/Wnt pathway...