Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Staurosporine is an antibiotic that specifically inhibits protein kinase C. Fourteen staurosporine- and temperature-sensitive (stt) mutants of Saccharomyces cerevisiae were isolated and characterized. These mutants were divided into ten complementation groups, and characterized for their cross-sensitivity to K-252a, neomycin, or CaCl2. The STT1 gene was cloned and sequenced. The nucleotide sequence of the STT1 gene revealed that STT1 is the same gene as PKC1. The STT1 gene conferred resistance to staurosporine on wild-type cells, when present on a high copy number plasmid. STT1/stt1::HIS3 diploid cells were more sensitive to staurosporine than STT1/STT1 diploid cells. Analysis of temperature-sensitive stt1 mutants showed that the STT1 gene product functioned in S or G2/M phase. These results suggest that a protein kinase (the STT1 gene product) is one of the essential targets of staurosporine in yeast cells.
Mol Gen Genet 1992 Feb
PMID:Characterization of a staurosporine- and temperature-sensitive mutant, stt1, of Saccharomyces cerevisiae: STT1 is allelic to PKC1. 153 90

We have previously suggested that two positioned nucleosomes are removed from the promoter of the Saccharomyces cerevisiae SUC2 gene upon depression by glucose starvation. To gain further insight into the changes accompanying derepression at the chromatin level we have studied the chromatin structure of the SUC2 promoter in several mutants affecting SUC2 expression. The non-derepressible mutants snf1, snf2 and snf5 present a chromatin structure characteristic of the repressed state, irrespective of the presence or absence of glucose. The non-repressible mutants, mig1 and ssn6, as well as the double mutant snfs sn6 exhibit an opened chromatin structure even in the presence of glucose. These results suggest that the DNA-binding protein encoded by MIG1 is necessary to produce the characteristic pattern of repressed chromatin and that the SNF1 protein kinase is sufficient to produce the derepressed chromatin pattern. A model is presented for the transitions that result in opening up of the chromatin structure.
Mol Gen Genet 1992 Feb
PMID:Chromatin structure of the yeast SUC2 promoter in regulatory mutants. 153 95

Both PHO80 and PHO85 genes are required to establish the repressed state of the PHO system of Saccharomyces cerevisiae. S1 nuclease protection analysis of the PHO85 transcript revealed that the PHO85 gene contains an intron at the 6th codon of the gene. Each of the fusion proteins, LacZ-Pho80 and LacZ-Pho85, was produced into Escherichia coli and used as an antigen to raise antibodies in a rabbit. Using the affinity-purified antibodies in Western blotting experiments, the PHO85 protein was detected as a 36 kDa and the PHO80 protein as a 34 kDa protein. The PHO80 protein was detected only in extracts prepared from an overproducing strain. The immunoprecipitate containing the PHO85 protein showed protein kinase activity suggesting that PHO85 is a protein kinase gene, which is consistent with the observation that the deduced amino acid sequence of the PHO85 protein resembles that of some protein kinases. The PHO80 protein was found to be phosphorylated in the presence of PHO85 protein.
Mol Gen Genet 1992 Feb
PMID:Negative regulators of the PHO system of Saccharomyces cerevisiae: characterization of PHO80 and PHO85. 153 98

The mechanism of activation of KCl cotransport has been examined in rabbit red blood cells. Previous work has provided evidence that a net dephosphorylation is required for activation of transport by cell swelling. In the present study okadaic acid, an inhibitor of protein phosphatases, was used to test this idea in more detail. We find that okadaic acid strongly inhibits swelling-stimulated KCl cotransport. The IC50 for okadaic acid is approximately 40 nM, consistent with the involvement of type 1 protein phosphatase in transport activation. N-Ethylmaleimide (NEM) is well known to activate KCl cotransport in cells of normal volume. Okadaic acid, added before NEM, inhibits the activation of transport by NEM, indicating that a dephosphorylation is necessary for the NEM effect. Okadaic acid added after NEM inhibits transport only very slightly. After a brief exposure to NEM and rapid removal of unreacted NEM, KCl cotransport activates with a time delay that is similar to that for swelling activation. Okadaic acid causes a slight increase in the delay time. These findings are all consistent with the idea that NEM activates transport not by a direct action on the transport protein but by altering a phosphorylation-dephosphorylation cycle. The simplest hypothesis that is consistent with the data is that both cell swelling and NEM cause inhibition of a protein kinase. Kinase inhibition causes net dephosphorylation of some key substrate (not necessarily the transport protein); dephosphorylation of this substrate, probably by type 1 protein phosphatase, causes transport activation.
J Gen Physiol 1991 Apr
PMID:Okadaic acid inhibition of KCl cotransport. Evidence that protein dephosphorylation is necessary for activation of transport by either cell swelling or N-ethylmaleimide. 164 39

The existence of dihydropyridine receptor in crayfish striated muscle was proved by Northern blot analysis and 3H PN 200--110 binding. The alpha 1 subunit is encoded by a 8300 nt mRNA population and is expressed as 190 kD protein in crayfish T-tubular system, which binds 3H PN 200--110 (Bmax 1.5 +/- 0.4 pmol/mg protein and KD 6.2 +/- 0.8 nmol/l). The purified protein is phosphorylated by cAMP-dependent protein kinase. The dihydropyridine receptor in crayfish striated muscle also contains alpha 2 subunit, which on Northern blot gives the same signal as the alpha 2 subunit from rabbit skeletal muscle.
Gen Physiol Biophys 1991 Jun
PMID:The dihydropyridine receptor: expression of 190 kD alpha 1 subunit in crayfish muscle. 165 59

Somatostatin (SRIF) reduces growth hormone releasing hormone (GRF)-stimulated growth hormone (GH) release from avian and mammalian adenohypophyseal cells. The present studies examined the intracellular mechanisms mediating SRIF inhibition of GRF-stimulated GH release from chicken pituitary cells. Increases (P less than 0.05) in GH release were observed in the presence of (1) GRF; (2) the adenylyl cyclase stimulator, forskolin; (3) a cAMP analog, 8-bromo-cAMP; (4) the phosphodiesterase inhibitor 3-isobutyl-l-methyl-xanthine (IBMX) combined with GRF; (5) a tumor-promoting phorbol ester and protein kinase C activator, phorbol 12-myristate, 13-acetate (PMA); (6) a diacylglycerol analog, 1,2-dioctanoyl-glycerol (DiC8); and (7) a calcium ionophore, A23187, alone and in combination with PMA. Somatostatin (10 ng/ml) reduced the release of GH stimulated by GRF, forskolin, and 8-bromo cAMP and the GRF-provoked release of GH in the presence of IBMX (P less than 0.05). Somatostatin, however, did not influence GH release in the presence of the protein kinase C activators, PMA or DiC8, or the calcium ionophore A23187. These data suggest that SRIF inhibits GRF-provoked GH release by reducing the ability of the cAMP-protein kinase A but not of the calcium or protein kinase C intracellular message pathways to stimulate GH release.
Gen Comp Endocrinol 1991 Jan
PMID:Possible involvement of adenylyl cyclase-cAMP-protein kinase a pathway in somatostatin inhibition of growth hormone release from chicken pituitary cells. 170 26

These studies examined the cellular basis for the inhibitory effects of triiodothyronine (T3) on growth hormone-releasing factor (GRF)-evoked growth hormone (GH) release from chicken anterior pituitary cells in vitro. A primary monolayer culture of anterior pituitaries from 4- to 8-week-old White Leghorn cockerels was performed as previously described by this laboratory. Following a 72-hr preincubation period, cells were washed and incubated (2 hr) with either secretagogues or media alone (control). T3 (20 ng/ml) or vehicle was added to cells during both the preincubation (48-72 hr) and incubation (2 hr period. Triiodothyronine reduced (P less than 0.05) GH release (ng/ml) in response to (1) GRF; (2) the adenylyl cyclase stimulator, forskolin; (3) the cAMP analog and protein kinase A activator, 8-bromo cAMP; and (4) the phorbol ester and protein kinase C activator, phorbol 12-myristate 13-acetate. Triiodothyronine reduced (P less than 0.05) the intracellular content of GH and total GH (released GH and intracellular GH) irrespectively of whether secretagogues were also present. When GH release was expressed as a percentage of total GH [released GH/(intracellular GH + released GH)], percentage GH released in response to GRF, or the protein kinase A, protein kinase C, or calcium pathway activators was not as great in T3-treated versus non-T3-treated cells. These data indicate that T3 inhibits GRF-evoked GH release by reducing the availability of intracellular stores of GH and by also inhibiting second messenger-stimulated GH release pathways.
Gen Comp Endocrinol 1991 Dec
PMID:Triiodothyronine (T3) inhibition of growth hormone secretion by chicken pituitary cells in vitro. 172 15

The deduced amino acid sequences of the open reading frames (ORFs) mapping in the short unique segment (US) of Marek's disease virus (MDV) reported in the accompanying paper have been analysed using computer programs to determine their relationships to herpesvirus proteins. Analysis of the catalytic domains of protein kinases showed that the MDV kinase (MDV PK) was closely related to the alphaherpesvirus protein kinase mapping in US. The results also showed that the MDV PK was more closely related to the cellular kinases that control cell division than to the proto-oncogenes c-src and c-mos and it was predicted that the MDV PK would phosphorylate serine/threonine. The MDV homologue of herpes simplex virus (HSV) glycoprotein D (gD) contained several residues that were conserved in mammalian herpesviruses. In particular, six cysteines were perfectly aligned in all the gDs and there were numerous conservative substitutions. Although only approximately 65% of the MDV homologue of glycoprotein I (gI) of HSV has been sequenced, it was clear that a significant number of amino acid residues including four cysteines were conserved in the gI homologues of MDV and mammalian herpesviruses. Further analysis suggested that MDV gD was more closely related to the gDs of pseudorabies virus (PRV) and equine herpesvirus 1 than to the gD of HSV-1 and HSV-2. It was noted that HSV-2 glycoprotein G (gG), PRV gX and MDV gD were related and that MDV ORF4 was related to MDV gD and probably to HSV-1 gG. The results have shown a clear relationship between the genes of MDV and their counterparts in mammalian alphaherpesviruses and are consistent with the idea that MDV glycoprotein genes in US might have arisen by a process of gene duplication and independent evolution.
J Gen Virol 1991 Apr
PMID:Properties and evolutionary relationships of the Marek's disease virus homologues of protein kinase, glycoprotein D and glycoprotein I of herpes simplex virus. 184 76

The DNA sequence of a 5.5 kbp EcoRI fragment located in the short unique region (US) of the 'highly oncogenic' strain RB1B of Marek's disease virus (MDV) was determined. The sequence contained six open reading frames (ORFs), four of which were homologous to proteins mapping in the US region of herpes simplex virus type 1 (HSV-1). These include the homologues of HSV-1 protein kinase, glycoprotein D (gD), glycoprotein I (gI) and US2 which is of unknown function. The MDV ORFs had a marked bias for A or T in the third codon position and analysis of the dinucleotide frequencies showed a marginal deficit in ApG/CpT but no overall deviation of CpG from random expectations. Comparison of genes in the US region of MDV to herpesvirus proteins confirmed and extended our previous observation that MDV is more closely related to alphaherpesviruses than to gamma-herpesviruses. We also showed that MDV possessed a homologue of HSV-1 gD which is lacking in varicella-zoster virus (VZV) but that MDV probably lacked homologues of US4 and US5 of HSV-1. These results show that in contrast to the genes in the long unique region which were grossly collinear in HSV, VZV and MDV, those mapping in US show greater diversity.
J Gen Virol 1991 Apr
PMID:DNA sequence and organization of genes in a 5.5 kbp EcoRI fragment mapping in the short unique segment of Marek's disease virus (strain RB1B). 184 77

The product of the CDC7 gene of Saccharomyces cerevisiae has multiple cellular functions, being needed for the initiation of DNA synthesis during mitosis as well as for synaptonemal complex formation and commitment to recombination during meiosis. The CDC7 protein has protein kinase activity and contains the conserved residues characteristic of the protein kinase catalytic domain. To determine which of the cellular functions of CDC7 require this protein kinase activity, we have mutated some of the conserved residues within the CDC7 catalytic domain and have examined the ability of the mutant proteins to support mitosis and meiosis. The results indicate that the protein kinase activity of the CDC7 gene product is essential for its function in both mitosis and meiosis and that this activity is potentially regulated by phosphorylation of the CDC7 protein.
Mol Gen Genet 1991 Jul
PMID:CDC7 protein kinase activity is required for mitosis and meiosis in Saccharomyces cerevisiae. 186 80


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>