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)

In a genetic screen for second-site mutations that are lethal in combination with a deletion of the amino terminus of histone H3, we have uncovered three new gene products that regulate the Saccharomyces cerevisiae Swe1 kinase. The Swe1 protein kinase phosphorylates tyrosine residue 19 of Cdc28 and inhibits its activity. One histone synthetic-lethal gene, HSL1, encodes a putative protein kinase that has high sequence and functional homology to fission yeast cdr1/nim1, an inhibitory kinase of wee1. Another gene, HSL7, is a novel negative regulator of Swe1 function. Sequences similar to Hsl7 exist in Caenorhabditis elegans and humans. In addition, we have isolated a dosage-dependent suppressor, OSS1, of hsl1 and hsl7. OSS1 is important for the transcriptional repression of SWE1 and CLN2 in G2. Mutations in HSL1 and HSL7 therefore cause hyperactivity of the Swe1 kinase, which in turn decreases mitotic Cdc28 kinase activity. Moreover, HSL5 is identical to CDC28, further suggesting that it is the decreased Cdc28 kinase activity in these hsl mutants that causes lethality in the histone mutant background. Because neither HSL1 nor HSL7 is essential in yeast, and histone transcription is unaffected by the hsl5/cdc28 mutation, it is unlikely that synthetic lethality results from reduced transcription of HSL1 and HSL7 caused by histone mutations, or from reduced histone transcription when Cdc28 kinase activity is compromised. We suggest that these cell cycle regulators function in a pathway upstream of both histones H3 and H4, thereby modulating histone function in the cell cycle.
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PMID:A search for proteins that interact genetically with histone H3 and H4 amino termini uncovers novel regulators of the Swe1 kinase in Saccharomyces cerevisiae. 864 31

The effects of pkadaic acid (OKA) and calyculin A (CLA), inhibitors of protein phosphatases type 1 (PrPase1) and type 2A (PrPase2A), an acid secretion were examined in rabbit isolated gastric gland, CLA, but not OKA, strongly stimulated acid secretion by itself without affecting glandular adenosine 3',5'-cyclic monophosphate (cAMP) contents. CLA-induced secretion was suggested to be mainly due to the increase in the phosphorylation of protein kinase A substrates via the inhibition of PrPase1 in the parietal cell, since 1) CLA-induced secretion was not inhibited by cimetidine or atropine, 2) a protein kinase A inhibitor inhibited the secretion, whereas a protein kinase C inhibitor did not, 3) CLA augmented dibutyryl cAMP-induced secretion in some cases, and 4) OKA, which is 100 times more selective to PrPase2A than to PrPase1, was not a secretagogue. Unexpectedly, CLA did not augment the secretion by histamine, possibly because the inhibitor augmented the phosphorylation-mediating negative feedback pathway as well. Both CLA and OKA markedly increased phosphorylation of ezrin, a putative protein kinase A substrate, in the course of secretory activation.
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PMID:Calyculin A, a phosphoprotein phosphatase inhibitor, stimulates acid secretion in isolated gastric glands. 877 7

The CLK1 gene of Saccharomyces cerevisiae encodes a 610-residue protein kinase that resembles known type II Ca2+/calmodulin-dependent protein kinases (CaM kinases), including the CMK1 and CMK2 gene products from the same yeast. The Clk1 kinase domain is preceded by a 162-residue N-terminal extension, followed by a 132-residue C-terminal extension (which contains a basic segment resembling known calmodulin-binding sites) and is as similar to mammalian CaM kinase (38% identity to rat CaM kinase alpha) as it is to yeast CaM kinase (37% identity to Cmk2). However, Clk1 shares 52% identity with Rck1, another putative protein kinase encoded in the S. cerevisiae genome. Clk1 tagged with a c-myc epitope (expressed in yeast) and a GST-Clk1 fusion (expressed in bacteria) underwent autophosphorylation and phosphorylated an exogenous substrate (yeast protein synthesis elongation factor 2), primarily on Ser. Neither Clk1 activity was stimulated by purified yeast calmodulin (CMD1 gene product), with or without Ca2+; no association of Clk1 with Cmd1 was detectable by other methods. C-terminally truncated Clk1(Delta487-610) was growth-inhibitory when overexpressed, whereas catalytically inactive Clk1(K201R Delta487-610) was not, suggesting that the C terminus is a negative regulatory domain. Using immunofluorescence, Clk1 was localized to the cytosol and excluded from the nucleus. A clk1Delta mutant, a clk1Delta rck1Delta double mutant, a clk1Delta cmk1Delta cmk2Delta triple mutant, and a clk1Delta rck1Delta cmk1Delta cmk2Delta quadruple mutant were all viable and manifested no other overt growth phenotype.
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PMID:Identification and characterization of the CLK1 gene product, a novel CaM kinase-like protein kinase from the yeast Saccharomyces cerevisiae. 893 41

The oxime derivative 2,3-butanedione monoxime (BDM) is used as an inorganic phosphatase to probe the phosphorylation state of many cellular proteins including the L-type calcium channel in various tissues. We used BDM further to shed light on the controversy surrounding direct phosphorylation of the L-type Ca2+ channel. We employed a recombinant system that utilizes HEK 293 cells expressing wild type and mutant human heart calcium channels. BDM reversibly reduced the calcium channel current induced by expression of the wild type channel in a concentration-dependent manner with an apparent IC50 value of 15.3 mM. Deletion of part of the carboxyl terminus of the alpha 1 subunit, which contains one putative protein kinase A site, or mutating all of the protein kinase A consensus sites of the pore forming subunit, did not significantly change the apparent IC50 value or alter in any other way the blocking effect of BDM on the expressed currents. Our data suggest that BDM produces reversible modifications of the cardiac calcium channel protein leading to an expected reduction in the amplitude of the expressed currents, but the site of action must be different from that of the consensus sites for protein kinase A dependent phosphorylation.
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PMID:Inhibition of cloned human L-type cardiac calcium channels by 2,3-butanedione monoxime does not require PKA-dependent phosphorylation sites. 901 46

Protein kinase activities in myxoamoebae of a true slime mold, Physarum polycephalum, were investigated in response to heat shock. In-gel assay detected an apparent activation of a Ca(2+)-dependent, 53-kDa protein kinase that phosphorylated casein but not histone H1. This enzyme needed co-presence of Mg2+ ion with Ca2+ for activity. Treatment with calf intestinal alkaline phosphatase did not affect the heat-inducible 53-kDa protein kinase activity at all. The effects of protein kinase inhibitors were examined, and staurosporine suppressed the activity of this enzyme completely. H-7 decreased the activity to about 20% and HA-1004 to 65%. These results suggest that this protein kinase that may phosphorylate tyrosine and serine/threonine residues of target proteins is activated by heat shock in Physarum cells, and the activation is not regulated via phosphorylation by putative protein kinase(s) that may act at an upstream position in the signaling cascade(s).
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PMID:Activation of a Ca(2+)-dependent protein kinase in response in heat shock in the myxoamoebae of a true slime mold, Physarum polycephalum. 907 11

Sequence analysis of an 11,628 bp DNA segment from the right arm of Saccharomyces cerevisiae chromosome VII revealed the presence of the 5' end of the RAD2 gene, the MES1 gene and six open reading frames (ORFs) each longer than 300 bp. Four of these ORFs are expressed genes, as indicated by transcript analysis. One of them, YGR261c, which specifies a putative beta-adaptine, corresponds to gene YKS5, which has recently been identified as a suppressor of loss of casein kinase 1 function. The remaining three ORFs are new genes; of these, YGR260w encodes a protein showing similarity to the S. cerevisiae allantoate permease and YGR262c specifies a putative protein kinase.
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PMID:Analysis of an 11.6 kb region from the right arm of chromosome VII of Saccharomyces cerevisiae between the RAD2 and the MES1 genes reveals the presence of three new genes. 909 59

When phosphorylated, the inhibitory subunit of troponin (TnI) causes a loss in calcium sensitivity and a decrease in actomyosin ATPase. To examine this process, we bacterially expressed wild type TnI and TnI mutants in which serine 22 and 23, a putative protein kinase A (PKA) site, and threonine 143, a putative protein kinase C (PKC) site, were replaced by alanine S22A/23A and TI43A. PKA dependent phosphorylation was approximately 90% reduced in the S22A/23A mutant and unaffected in T143A. PKC dependent phosphorylation was markedly reduced in T 143A relative both to a wild type construct and to S22A/23A, although some residual phosphorylation (likely at sites other than T143) was seen. The calcium sensitivity (i.e. inhibition of actomyosin ATPase in the presence of EGTA) and regulation of the reconstituted actomyosin system was preserved in the absence of phosphorylation using wild type TnI or either mutant. Calcium sensitivity was decreased by both PKA and PKC with the wild type TnI but was unaffected by PKA when the S22A/23A mutant was employed and by PKC when the T143A mutant was reconstituted. The calcium dependency of the ATPase curve was substantially right shifted when PKC phosphorylated wild type TnI was employed for regulation, and this was markedly attenuated when T143 A was reassociated (although a slight rightward shift and a reduction in maximal ATPase activity was still seen). These data confirm that phosphorylation of TnI by regulatory kinases plays a major role in the regulation of myofibrillar ATPase. The N-terminal serines (22 and 23) appear to be uniquely important for the PKA response whereas threonine 143 is involved in the PKC response although other residues may also have functional significance.
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PMID:Expression and regulation of mutant forms of cardiac TnI in a reconstituted actomyosin system: role of kinase dependent phosphorylation. 914 23

Monoclonal antibody raised against a preparation of loach fish sperm centrosomes was used for screening of cDNA expressing library of Chinese hamster CHO-K1 cells. Two positive clones appeared to encode 628 amino acid protein fragment that was 72% identical to human KIAA0204 protein, i.e. putative protein kinase. Polyclonal antibodies raised against products of cDNA expression in E. coli recognized 210-kDa polypeptide in CHO-K1 cells and immunostained nuclear speckles, centrosomes and microtubules in these cells. The 210-kDa polypeptide (named MAK-L) co-sedimented with exogenous microtubules. Thus, one more protein kinase seems to be associated with the microtubule network in vertebrate cells.
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PMID:Chinese hamster protein homologous to human putative protein kinase KIAA0204 is associated with nuclei, microtubules and centrosomes in CHO-K1 cells. 930 47

Saccharomyces cerevisiae YGR262c gene, whose disruption causes severely defective growth, encodes a putative protein kinase shorter than any other protein kinase biochemically characterized to date and lacking some of the conserved features of these enzymes. Here we show that the product of the YGR262c gene, piD261, expressed in E. coli with a C-terminal (His)6 tag, is a bona fide Ser/Thr protein kinase as judged from its capability to autophosphorylate and to phosphorylate casein and osteopontin in the presence of [gamma-32P]ATP. In contrast, no phosphorylation of histones, myelin basic protein, phosvitin, bovine serum albumin and poly(Glu/Tyr)4:1 could be detected. Mn2+ or, less effectively, Co2+ are required for piD261 catalytic activity, which is conversely undetectable in the presence of Mg2+, a behaviour unique among Ser/Thr protein kinases.
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PMID:Biochemical evidence that Saccharomyces cerevisiae YGR262c gene, required for normal growth, encodes a novel Ser/Thr-specific protein kinase. 930 53

Since various secretory stimuli regulate not only secretion but also protein, RNA, and DNA syntheses in salivary glands, we evaluated the effect of secretory stimuli on the phosphorylation state of CREB (cAMP response element-binding protein). Isoproterenol, forskolin, and CPS-cAMP markedly stimulated the phosphorylation of CREB in parotid acinar cells, and PKA inhibitors H-8 and H-89 dose-dependently inhibited it. In contrast, carbachol (CCH) and A23187 decreased CREB phosphorylation, but CCH did not decrease it in the absence of extracellular Ca2+. Although protein phosphatase inhibitor calyculin A alone markedly increased the phosphorylation, it could not prevent CCH-induced dephosphorylation of CREB. CaM kinase IV, a putative protein kinase for CREB in response to Ca2+ elevation, was undetectable in parotid acinar cells.
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PMID:Regulation of CREB phosphorylation by cAMP and Ca2+ in parotid acinar cells. 935 75


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