Disease relevance of Csnk1a1

• L. major CK1 isoform 2 expressed as a recombinant protein in Escherichia coli displayed biochemical and inhibition characteristics similar to those of the purified native enzyme [1].
• Pretreatment of leishmania homologue of receptors for activated C kinase (LACK) promotes disease progression caused by Leishmania amazonensis [2].

High impact information on Csnk1a1

• cAMP-dependent protein kinase phosphorylation of the acid-sensing ion channel-1 regulates its binding to the protein interacting with C-kinase-1 [3].
• Here we report that both Cdk5 and CK1 are regulated by metabotropic glutamate receptors (mGluRs) in neostriatal neurons [4].
• (S)-3,5-dihydroxyphenylglycine (DHPG), an agonist for group I mGluRs, increased Cdk5 and CK1 activities in neostriatal slices, leading to the enhanced phosphorylation of Thr-75 and Ser-137 of DARPP-32, respectively [4].
• Casein kinase 1 (CK1) has been implicated in a variety of cellular functions such as DNA repair, circadian rhythm, and intracellular trafficking [4].
• In the neostriatum, CK1 has been found to phosphorylate Ser-137 of DARPP-32 [4].

Biological context of Csnk1a1

• Pretreatment of endothelial cells with the protein kinase CK1-specific inhibitor IC261 prevented the H(2)O(2)-stimulated phosphorylation of hnRNP-C [5].
• These results provide the first evidence for a role of CK1 in the regulation of synaptic transmission in the brain [6].
• This part of the kappa B site resembled sequences in the binding site for a second inducible nuclear factor of T cells, NF-AT, as well as a conserved sequence found in several lymphokine genes, termed "cytokine-1" (CK-1) [7].
• Competition and methylation interference analysis showed that both NF-AT and CK-1 sequences bound a factor similar to the novel kappa B-binding factor and that binding involved a four-nucleotide sequence (TTCC) that the kappa B, CK-1, and NF-AT sites have in common [7].
• Inhibition by staurosporine derivatives of cyclic AMP-dependent protein kinase (A-kinase) and protein kinase C (C-kinase), and drug resistance has been investigated [8].

Anatomical context of Csnk1a1

• These results raise the possibility that related factors binding to kappa B, CK-1, and NF-AT sequences could play a role in the coordinate induction of T cell activation genes [7].
• The receptor for activated C kinase-1 was also found to associate with the spectrin-based cytoskeleton [9].
• Casein kinase 1 (CK1) is a family of multifunctional Ser/Thr protein kinases that are ubiquitous in eukaryotic cells [1].

Associations of Csnk1a1 with chemical compounds

• In the present study, we show that CK1 regulates fast synaptic transmission mediated by glutamate, the major excitatory neurotransmitter in the brain [6].
• Indeed, inhibition of CK1 increases NMDA-mediated EPSCs in medium spiny striatal neurons [6].
• Casein kinase 1 (CK1) is a highly conserved serine/threonine kinase, present in virtually all cell types, in which it phosphorylates a wide variety of substrates [6].
• In addition, our results suggest that kappa B and CK-1 sites represent potential cyclosporin-sensitive promoter elements by virtue of their ability to bind an NF-AT-like factor [7].
• Biochemical studies have led to the unexpected discovery that an isoform of CK1 represents the primary target of the pyrrole and imidazopyridine kinase inhibitors in these organisms [1].

Other interactions of Csnk1a1

• Through the use of CK1 inhibitors, we present evidence that activation of CK1 decreases NMDA receptor activity in the striatum via a mechanism that involves activation by this kinase of protein phosphatase 1 and/or 2A and resultant increased dephosphorylation of NMDA receptors [6].
• Furthermore, all these molecules (spectrin, PKC beta, PKC theta, and receptor for activated C kinase-1) cotranslocate to the uropod [9].
• Protein interacting with C-kinase 1/protein kinase Calpha-mediated endocytosis converts netrin-1-mediated repulsion to attraction [10].

Analytical, diagnostic and therapeutic context of Csnk1a1

• The results described here warrant further evaluation of the activity of these kinase inhibitors against mammalian stage Leishmania parasites in vitro and in animal models of infection, as well as studies to genetically validate CK1 as a therapeutic target in trypanosomatid parasites [1].
• Further purification of CK1 activity from L. major and characterization via liquid chromatography coupled tandem mass spectrometry identified CK1 isoform 2 as the specific parasite protein inhibited by imidazopyridines [1].
• A cDNA coding Leishmania homologue of receptors for activated C kinase (LACK), which was known to play an important role in the early phase of Leishmania infection, was molecularly cloned from Leishmania amazonensis promastigote by using reverse transcription and nested polymerase chain reaction, and was sequenced [2].

References