Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have purified casein kinase I (CKI) over 6000-fold from bovine thymus and have sequenced seven tryptic peptides that account for nearly 25% of the primary sequence of the enzyme. By using PCR, partial cDNAs encoding CKI and a related enzyme (CKI-delta) were isolated. A product that may correspond to an alternatively spliced form of CKI was also detected. The CKI PCR product was used to probe a bovine brain cDNA library from which cDNAs corresponding to CKI (CKI-alpha) and two homologous enzymes (CKI-beta and CKI-gamma) were identified. The finding that there are at least four CKI-like enzymes suggests that CKI activity in tissues or cell extracts may be composed of multiple related but distinct protein kinases. This group of enzymes is not similar to any other known protein kinases and may, therefore, represent an additional branch of the protein kinase family.
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PMID:Purification of casein kinase I and isolation of cDNAs encoding multiple casein kinase I-like enzymes. 194 67

The enzyme termed nowadays protein kinase CK2 was first described in liver extracts (as a mixture with protein kinase CK1), using casein as artificial substrate, by Burnett and Kennedy (1954). In 1960 it was shown that such casein/phosvitin phosphorylating activity was ubiquitous and distinct from phosphorylase kinase, i.e., the only other protein kinase known at that time. CK1 and CK2 were distinguished from each other at the end of the sixties, and during the seventies CK2 was purified to homogeneity in several laboratories and thoroughly characterized as far as its subunit structure (alpha 2 beta 2), site specificity, and in vitro responsiveness to various effectors were concerned. The first endogenous substrate for CK2 (eIF-3) was described in 1976, but it was during the eighties that it became clear that CK2 is a pleiotropic protein kinase committed with the phosphorylation of a myriad of cellular targets. More than 100 CK2 substrates are known, sharing typical phosphoacceptor sites specified by multiple acidic residues on the C terminal side of Ser/Thr. The definition of the primary structure of CK2 catalytic subunit, in 1987, definitely included CK2 in the big family of eukariotic protein kinases. The growing interest for CK2 is accounted for by its unusual properties, by the increasing number of its substrates, and by several coincidental arguments suggesting that this pleiotropic protein kinase plays a fundamental role in cellular regulation. A major and intriguing problem concerning CK2 is its apparent lack of regulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A historical view of protein kinase CK2. 773 12

A cDNA clone coding for human protein kinase CK1 (casein kinase 1) has been isolated and sequenced demonstrating that it corresponds to a homolog of the CK1 alpha form found in bovine brain. The derived amino acid sequence of the human CK1 alpha is identical to the bovine counterpart except that it contains 12 extra amino acids at the carboxyl end. Using this cDNA sequence and PCR amplification, YAC genomic clones that contain this human CK1 alpha sequence have been isolated. These YACs have been used for fluorescent in situ hybridization in order to localize the human CK1 alpha gene to chromosome 13q13.
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PMID:Cloning and chromosomal localization of the gene coding for human protein kinase CK1. 805 May 87

We examined the androgenic regulation of protein kinase CK1 in rat ventral prostate cytosolic and chromatin fractions. On androgen deprivation, CK1 in both the nuclear and cytoplasmic compartments decreases slowly at a similar rate. Stimulation of regrowth in the prostate does not evoke an early differential modulation in the CK1 because it increased in both the cytosol and chromatin only by 24 h after androgenic stimulus. These changes in CK1 relate to its proposed role in cell regulation at mitosis and differ from those in protein kinase CK2 that demonstrates rapid modulations in the nuclear compartment under similar conditions.
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PMID:Androgenic regulation of protein kinase CK1 in the prostatic cell. 886 89

Using immunoblot and immunofluorescence analysis with a cross-reacting antiserum, we identified Xenopus laevis occludin as a 57-61 kDa antigen colocalized with cingulin in epithelial junctions of embryos. Occludin was completely extracted from unfertilized eggs and embryos with a solution containing 0.1% Triton X-100 and 1% NP40. Maternal occludin in unfertilized eggs migrated by SDS-PAGE as a 61 kDa protein. In fertilized eggs and in early cleavages up to blastula stage 8 it migrated as a series of polypeptides with 57-60 kDa. In gastrulae, neurulae and tailbud stage embryos, it migrated as a 57 kDa polypeptide. The electrophoretic mobility downshift was specifically reproduced by treatment of extracts with acid phosphatase, indicating that it is due to dephosphorylation. The correlation of occludin dephosphorylation with the de novo assembly of tight junction in native epithelia of Xenopus embryos suggests a possible role of occludin dephosphorylation in the events leading to tight junction assembly. To identify kinases which can phosphorylate occludin, recombinant chicken occludin (cytoplasmic domain) was subjected to in vitro phosphorylation. Occludin was phosphorylated on serine and threonine residues by protein kinase CK2 and p34cdc2/cyclin B complex, but was not significantly phosphorylated by mitogen-activated protein kinase, protein kinase CK1 and p38Syk tyrosine kinase. We noted that occludin sequences contain a motif matching the activation loop of the cytoplasmic domain of insulin receptor kinase.
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PMID:Occludin dephosphorylation in early development of Xenopus laevis. 936 83

A variety of synthetic peptides derived from either the inhibitor-2 (I-2) phosphoacceptor sites or the optimal sequences selected in an oriented peptide library have been compared for their susceptibility to phosphorylation by protein kinase CK1 (also termed casein kinase-1). The I-2-derived peptides are by far preferred over the library peptides by both rat liver CK1 (and by the alpha/beta, gamma and delta/epsilon isoforms immunoprecipitated from it) and recombinant Xenopus laevis CK1 alpha. The superiority of the I-2-derived peptides over the library ones is reflected by Vmax values one to two orders of magnitude higher while the Km values are comparable. Individual substitutions of any of the aspartic acids with alanine in the I-2-derived peptide RRKHAAIGDDDDAYSITA is detrimental, producing both a fall in Vmax and an increase in Km which are more pronounced at position n -3, but also quite significant at positions n -4, n -5 and, to a lesser extent, n -6. The unfavourable effect of these substitutions is more evident with rat liver CK1 than with recombinant Xenopus laevis CK1 alpha. The chimeric peptide IGDDDDAY-S-IIIFFA, resulting from the combination of the N-terminal acidic sequence of the I-2 (Ser86) site and the C-terminal hydrophobic cluster selected in the library peptides (MAEFDTG-S-IIIFFAKKK and MAYYDAA-S-IIIFFAKKK) is phosphorylated as efficiently as the I-2-derived peptide in terms of both Km and Vmax. These combined data strongly support the conclusion that, at variance with the optimal sequences selected in the library, optimal non-phosphate-directed phosphorylation of peptide substrates by CK1 critically relies on the presence of a cluster of acidic residues (preferably aspartic acid) upstream from position n -2, while the highly hydrophobic region downstream from serine selected in the library appears to be dispensable. The reason for these discrepancies remains unclear. The possibility that the library data are biased by the invariant elements forming its scaffold (MA-x-x-x-x-x-SI-x-x-x-x-AKKK) would be consistent with the observation that the library-selected peptides, despite their low Km values, fail to compete against the phosphorylation of protein and peptide substrates by CK1, suggesting that they bind to elements partially distinct from those responsible for substrate recognition.
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PMID:Optimal sequences for non-phosphate-directed phosphorylation by protein kinase CK1 (casein kinase-1)--a re-evaluation. 1009 90

The lens fiber cell-specific gap junction protein connexin49 is a substrate for a membrane-associated Ser/Thr protein kinase that can be extracted from lens cell membranes by 0.6 M KCl. However, the identity of this protein kinase has not been defined. In this report, evidence is presented indicating that it is casein kinase I. Thus, connexin49 was shown to be a substrate for purified casein kinase I but not for casein kinase II; the endogenous connexin49 protein kinase activity extracted from lens membranes with KCl was inhibited by the casein kinase I-specific inhibitor, N-(2-aminoethyl)-5-chloroisoquinoline-8-sulfonamide (CKI-7); the connexin49 protein kinase activity in the lens membrane KCl extract, which could be partially purified by gel filtration and affinity purification with a casein-Sepharose 4B column, copurified with casein kinase activity; phosphopeptide analysis showed that casein kinase I and the connexin49 protein kinase activity in the lens membrane KCl extract probably share the same phosphorylation sites in connexin49. Reverse transcription-PCR using total ovine lens RNA and casein kinase I isoform-specific oligonucleotide primers resulted in the amplification of cDNAs encoding casein kinase I-alpha and -gamma, while an in-gel casein kinase assay indicated casein kinase activity in the lens membrane KCl extract was associated with a major 39.2-kDa species, which is consistent with the 36 to 40-kDa size of casein kinase I-alpha in other animal species. These results demonstrate that the protein kinase activity present in the lens membrane 0.6 M KCl extract that catalyzes the phosphorylation of connexin49 is casein kinase I, probably the alpha isoform.
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PMID:Endogenous casein kinase I catalyzes the phosphorylation of the lens fiber cell connexin49. 1042 14

The phosphorylation and dephosphorylation of the NF-AT family of transcription factors play a key role in the activation of T lymphocytes and in the control of the immune response. The mechanistic aspects of NF-AT4 phosphorylation by protein kinase CK1 have been studied in this work with the aid of a series of 27 peptides, reproducing with suitable modifications the regions of NF-AT4 that have been reported to be phosphorylated by this protein kinase. The largest parent peptide, representing the three regions A, Z, and L spanning amino acids 173-218, is readily phosphorylated by CK1 at seryl residues belonging to the A2 segment, none of which fulfill the canonical consensus sequence for CK1. An acidic cluster of amino acids in the linker region between domains A and Z is essential for high-efficiency phosphorylation of the A2 domain, as shown by the increase in K(m) caused by a deletion of the linker region or a substitution of the acidic residues with glycines. Individual substitutions with alanine of each of the five serines in the A2 domain (S-177, S-180, S-181, S-184, and S-186) reduce the phosphorylation rate, the most detrimental effect being caused by Ser177 substitution which results in a 10-fold drop in V(max). On the contrary, the replacement of Ser177 with phosphoserine triggers a hierarchical effect with a dramatic improvement in phosphorylation efficiency, which no longer depends on the linker region for optimal efficiency. These data are consistent with a two-phase phosphorylation mechanism of NF-AT4 by CK1, initiated by the linker region which provides a functional docking site for CK1 and allows the unorthodox phosphorylation of Ser177; once achieved, this phosphoserine residue primes the phosphorylation of other downstream seryl residues, according to a hierarchical mechanism typically exploited by CK1.
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PMID:Structural features underlying the multisite phosphorylation of the A domain of the NF-AT4 transcription factor by protein kinase CK1. 1178 Nov 2

We isolated and sequenced a cDNA clone coding a human protein kinase CK1 (casein kinase 1) by screening a human fetal brain cDNA library. This new cDNA clone of 1756 bp contained an open reading frame, encoding a protein of 438 amino acids with a molecular weight of 50,272 Da and an isoelectric point of 9.37. The entire amino acid sequence of the novel human CK1 was 94% homologous to that of rat CK1gamma1. Northern blot analysis indicated that the human CK1gamma1 was highly expressed in the liver, skeletal muscle, heart and kidney. Furthermore, the human CK1gamma1 gene was mapped to chromosome 15q22 between STS marker D15S159 and D15S125 by polymerase chain reaction analysis of human/rodent hybrid cell panels.
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PMID:Molecular cloning, mapping and characterization of a human CK1gamma1 gene. 1211 64

Like the previously reported 4,5,6,7-tetrabromobenzotriazole (TBBt), the structurally related 4,5,6,7-tetrabromobenzimidazole (TBBz) is a selective ATP-competitive inhibitor of protein kinase CK2 from such divergent sources as yeast, rat liver, Neurospora crassa and Candida tropicalis, with K(i) values in the range 0.5-1 microM. It is virtually inactive vs. PKA, PKC, and a very weak inhibitor of protein kinase CK1. The corresponding tetrachlorobenzimidazole (TCBz) is a much weaker inhibitor of CK2, like tetrachlorobenzotriazole (TCBt) relative to TBBt. Bearing in mind the similarity of the van der Waals radii of Br (1.95 A) and CH(3) (2.0 A), the corresponding much less hydrophobic 4,5,6,7-tetramethylbenzotriazole (TMeBt) was prepared and found to be a very weak inhibitor of CK2, as well as of CK1. An unexpected, and significant, difference between TBBt and TBBz are their inhibitory activities vs. the yeast protein kinase PK60S, which phosphorylates, both in vitro and in intact yeast cells, three of the five pp13 kDa ribosomal surface acidic proteins in yeast cells. TBBt was previously noted to be a more effective inhibitor of PK60S than of yeast CK2; by contrast, TBBz is a relatively feeble inhibitor of PK60S, hence more selective than TBBt vs. CK2 in yeast cells. TMeBt was virtually inactive vs PK60S. Like TBBt, TBBz is an additional lead compound for development of more potent inhibitors of CK2.
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PMID:Selectivity of 4,5,6,7-tetrabromobenzimidazole as an ATP-competitive potent inhibitor of protein kinase CK2 from various sources. 1278 77


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