Disease relevance of Csnk1a1

• All three CK1 gamma isoforms were expressed as active enzymes in Escherichia coli and partially purified [1].
• Regulation of ornithine decarboxylase mRNA by phorbol esters and insulin in normal and C-kinase-deficient rat hepatoma cells [2].
• It is suspected that the suppression of insulin release from pancreatic islets by Vacor may contribute to the pathogenesis of Vacor-induced diabetes mellitus and that this suppression might not be related to cAMP and C-kinase [3].
• 1. Two kinds of C-kinase inhibitors were indicated to be present in mastocytoma cells [4].
• Phorbol ester treatment induced 5- to 10-fold increases in phosphorylation of the myristoylated alanine-rich C kinase substrate protein in muscle, whereas insulin and hypoxia had negligible effects [5].

High impact information on Csnk1a1

• Thus, activation of the Ca++-dependent enzyme, C kinase, modulates EGF receptor affinity, possibly via altered receptor phosphorylation [6].
• Reconstitution of unresponsive membranes with purified C kinase alters phosphorylation of the EGF receptor and restores the inhibitory effect of phorbol esters on 125I-EGF binding previously observed only in intact cells [6].
• Here we examine how glutamate receptor interacting protein (GRIP, also known as AMPAR binding protein or ABP) and protein interacting with C-kinase-1 (PICK) regulate subunit trafficking and plasticity [7].
• We investigated the role of MARCKS (myristoylated, alanine-rich C-kinase substrate) in dendrites of 3-week-old hippocampal cultures [8].
• Both 12-O-tetradecanoyl phorbol 13-acetate and 1,25(OH)2D3 activated endogenous PKC, as assessed by inhibition of myristoylated alanine-rich C kinase substrate back-phosphorylation by exogenous PKC [9].

Biological context of Csnk1a1

• Characterization of the genomic DNA flanking the exon unique to CKI alpha L demonstrated that CKI alpha and CKI alpha L arise by the alternative splicing of a common pre-mRNA molecule [10].
• Hydrolysis of PIP2 also produces DG, which has a messenger role in activating a specific protein kinase, the C kinase [11].
• ras-induced c-fos expression and proliferation in living rat fibroblasts involves C-kinase activation and the serum response element pathway [12].
• Pituitary C kinase might be involved in signal-transduction mechanisms in Gn-RH action, in particular, and in other hypophysiotropic hormones, in general, which operate by means of stimulation of phosphoinositide turnover during which diacylglycerol is liberated [13].
• To examine CK1 function, normal rat kidney cells were treated with CKI-7, and Cx43 content was analyzed by Triton X-100 extraction, cell-surface biotinylation, and immunofluorescence [14].

Anatomical context of Csnk1a1

• Several endogenous substrate proteins for C kinase ranging from 16 to 100 kDa were identified in pituitary cytosol [13].
• However, the beta-catenin sequence downstream from Ser-45 is very similar to a sequence recognized by CK1 in nuclear factor for activated T cells 4 [15].
• There is a strong correlation of beta-catenin mutations found in thyroid tumors with the motifs recognized by CK1 in this protein [15].
• The idea that the inhibition of synaptosome K channels by diC8 resulted from activation of C kinase was supported by pharmacological evidence [16].
• Using a partial cDNA fragment corresponding to an isoform termed CK1 gamma, three full-length rat testis cDNAs were cloned that defined three separate members of this subfamily [1].

Associations of Csnk1a1 with chemical compounds

• This inhibition is mediated by activation of cAMP-dependent kinase as it is prevented by pretreatment with the A-kinase inhibitor, N-[2-(methylamino)ethyl]-5-isoquinoline-sulfonamide (H8) but not by the C-kinase inhibitor, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7) [17].
• Pretreatment with either staurosporine, C-kinase inhibitor, or calmidazolium, a calmodulin inhibitor, partially prevented but, together, completely prevented the inhibitory effect of phenylephrine [18].
• Carbachol and the C kinase activator 120-tetradecanoylphorbol-13-acetate also stimulated histamine release [19].
• Hydrolysis of inositol phospholipids by receptor stimulation activates two separate signaling pathways, one leading to the activation of protein kinase C (C kinase) via formation of diacylglycerol [20].
• The C-kinase inhibitors chlorpromazine and trifluoperazine inhibit the phorbol diester stimulated phosphorylation of site T3 in a dose-dependent manner [21].

Regulatory relationships of Csnk1a1

• Involvement of protein kinase C epsilon in thyrotropin-releasing hormone-stimulated phosphorylation of the myristoylated alanine-rich C kinase substrate in rat pituitary clonal cells [22].
• We previously reported that a blockade of GnRH receptor activation inhibited the already-initiated C-kinase pathway(s) [23].

Other interactions of Csnk1a1

• In order to further evaluate the role of protein kinase C activation in glucose-induced insulin secretion, the extent of phosphorylation of the myristoylated alanine-rich C kinase substrate (MARCKS) was examined in freshly isolated rat pancreatic islets prelabeled with [32P]orthophosphate [24].
• Here we show that atrial KACh channels are assembled in a signaling complex with Gbetagamma, G protein-coupled receptor kinase, cyclic adenosine monophosphate-dependent protein kinase, two protein phosphatases, PP1 and PP2A, receptor for activated C kinase 1, and actin [25].
• For comparative purposes, the protein kinase C substrates myristoylated alanine-rich C kinase substrate-like protein and growth-associated protein-43 were examined in parallel [26].
• These data suggest that C-kinase might be a possible regulator of calcitonin secretion in addition to the cyclic AMP-mediated pathway [27].

Analytical, diagnostic and therapeutic context of Csnk1a1

• Cellular co-immunoprecipitation experiments and in vitro CK1 phosphorylation reactions indicate that CK1 interacted with and phosphorylated Cx43, initially on serine(s) 325, 328, or 330 [14].
• Immunofluorescence experiments in the presence of CK1 inhibitor showed increases in Cx43 plasma membrane localization but not necessarily accumulation at cell-cell interfaces [14].
• Microinjection of purified calcium phospholipid-dependent protein kinase (C-kinase) resulted in the rapid and transient induction of c-fos in quiescent rat embryo fibroblats [28].
• Myristoylated alanine-rich C kinase substrate messenger RNA exhibited a robust increase in both neurons and non-neuronal cells in the facial motor nucleus beginning four days after axotomy, peaked at seven days (2.5-fold), and declined back to baseline levels by 40 days [26].
• A broad area of C-kinase inhibitory activity was detected after DEAE-cellulose chromatography of 20,000 g supernatant of rat stomach homogenate [29].

References