Disease relevance of CkIalpha

• Transgenic mice ectopically expressing Cux-1 develop renal hyperplasia associated with the down-regulation of the CKI p27 [1].

High impact information on CkIalpha

• This was first shown in Drosophila with the characterization of Doubletime (Dbt), a homologue of vertebrate casein kinase Iepsilon [2].
• CKI and CKII mediate the FREQUENCY-dependent phosphorylation of the WHITE COLLAR complex to close the Neurospora circadian negative feedback loop [3].
• These results indicate that CKI functions as a negative regulator of Wg/Arm signaling [4].
• Overexpression of CKIalpha induced hyper-phosphorylation of both Arm and Dishevelled in S2R+ cells and, conversely, CKIalpha-RNAi reduced the amount of hyper-modified forms [4].
• His-tagged Arm was phosphorylated by CKIalpha in vitro on a set of serine and threonine residues that are also phosphorylated by Zeste-white 3 [4].

Biological context of CkIalpha

• CKI phosphorylation sites act cooperatively to promote Ci processing in vivo [5].
• We propose that phosphorylation of Ci by CKI creates multiple Slimb/beta-TRCP binding sites that act cooperatively to recruit SCF(Slimb/beta-TRCP) [5].
• Moreover, Drosophila embryos injected with CKIalpha double-stranded RNA showed a naked cuticle phenotype, which is associated with activation of Wg signaling [4].
• Drosophila doubletime mutations which either shorten or lengthen the period of circadian rhythms decrease the protein kinase activity of casein kinase I [6].
• Since the amino acid sequences and three-dimensional structures of Casein kinase I(delta)/(epsilon) enzymes are highly conserved, the results suggest that these proteins may also function in controlling cell growth and survival in other organisms [7].

Anatomical context of CkIalpha

• Here, we report that blocking CKI function inhibits embryonic morphogenesis and activates JNK in cell lines [8].
• Constitutive expression and delayed light response of casein kinase Iepsilon and Idelta mRNAs in the mouse suprachiasmatic nucleus [9].
• In situ hybridization showed presumably identical distribution of dbt, CKI[.alpha], and per transcripts in the putative clock neurons of the head ganglia, as well as in the retina, where CKI-and PER-like immunoreactivities were colocalized, suggesting a possible involvement of both CKIs in the B. mori circadian system [10].
• The circadian clock-containing photoreceptor cells in Xenopus laevis express several isoforms of casein kinase I [11].
• Pattern recognition analysis identifies cell attachment, glycosylation, myristoylation, microbody targeting, phosphorylation, cAMP/cGMP dependent, protein kinase C, casein kinase, and tyrosine kinase sites in these subunits [12].

Associations of CkIalpha with chemical compounds

• CKI phosphorylates Ci at three clusters of serine residues primed by PKA and GSK3 phosphorylation [5].

Enzymatic interactions of CkIalpha

• Casein kinase I phosphorylates the Armadillo protein and induces its degradation in Drosophila [4].
• CKI also phosphorylates and partially activates the transcription factor BMAL1 [13].

Regulatory relationships of CkIalpha

• In particular, whether Wg signaling suppresses CKIalpha- or Zw3-mediated Arm phosphorylation in vivo is unknown [14].

Other interactions of CkIalpha

• Here we show that Double-time (DBT)/CKIepsilon and CKIalpha act in conjunction to promote Ci processing [5].
• Hedgehog signalling activity of Smoothened requires phosphorylation by protein kinase A and casein kinase I [15].
• Phosphorylation of Dsh by CKI has also been suggested to switch its activity from noncanonical to canonical Wingless signaling [16].
• Surprisingly, CKIalpha- or CKIepsilon-RNAi markedly elevated the Armadillo (Arm) protein levels in Drosophila Schneider S2R+ cells, without affecting its mRNA levels [4].
• Casein kinase I (CKI) was recently reported as a positive regulator of Wnt signaling in vertebrates and Caenorhabditis elegans [4].

Analytical, diagnostic and therapeutic context of CkIalpha

• We report the molecular cloning and characterisation of the first CK1(casein kinase) gene of Drosophila melanogaster (dmCK1) [17].

References