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)

The amino-terminal domain of the large subunit of herpes simplex virus type 2 (HSV-2) ribonucleotide reductase (ICP10) has protein kinase (PK) activity and properties similar to those of growth factor receptor kinases which can be activated to transforming potential. DNA sequences that encode the PK domain cause neoplastic transformation of immortalized cells. The studies described in this report used a spontaneous mutant (ts5-152) temperature-sensitive for the synthesis of ICP10 and the previously described ICP10 expression vectors to study the role of ICP10 expression in HSV-2 growth and neoplastic potential. The titres of the ts5-152 mutant are 1000-fold lower at 39 degrees C compared to 34 degrees C after 12 h post-infection. The efficiency of plaquing is 0.003. The growth defect at 39 degrees C correlates with decreased ICP10 synthesis. Sequence analysis of the PK domain of the ts5-152 ICP10 gene identified a pair of frameshift mutations resulting in a 19 amino acid residue substitution at positions 275 to 293 and a downstream single base pair mutation causing a substitution at position 309. Cloning of the mutant ICP10 gene from ts5-152 into a wild-type HSV-2 isolate resulted in a recombinant (859/152) with growth properties and rates of ICP10 synthesis at 39 degrees C similar to those of ts5-152. Cells transformed with u.v.-inactivated ts5-152, or the recombinant 859/152, have significantly decreased cloning efficiency in agarose at 39 degrees C, but only during the first 250 post-transfer population doublings. Anchorage-independent growth was observed in cells transfected with expression vectors pJW17 or pJW32 that express ICP10 or its PK domain, respectively. Cells transfected with the frameshift mutant pJW21 or the ICP10 carboxy-terminal vector pJW31 did not form clones in agarose.
J Gen Virol 1992 Jun
PMID:Expression of the large subunit of herpes simplex virus type 2 ribonucleotide reductase (ICP10) is required for virus growth and neoplastic transformation. 131 43

Vesicular stomatitis virus (VSV) fails to replicate in mouse T lymphocytes unless the cells have been mitogenically stimulated with concanavalin A (Con A). We have examined the possibility that the failure of VSV to replicate in unstimulated T lymphocytes can be attributed to a deficiency in a host protein kinase which activates the viral P protein by phosphorylation, thus rendering it transcriptionally competent. Soluble extracts were prepared from purified mouse T lymphocytes, with or without prior treatment with Con A. The ability of these extracts to phosphorylate bacterially synthesized P protein of two VSV serotypes was measured in vitro. Activity of the protein kinase on the P proteins of the Indiana or New Jersey serotypes of VSV increased, on average 2.4- and 2.1-fold respectively, after treatment of the cells with 3 micrograms/ml Con A. Higher concentrations of Con A induced proportional increases (up to 10-fold) in the activity of the host protein kinase. Activities of the kinase phosphorylating the P protein in separate populations of CD4- and CD8-containing murine T lymphocytes increased similarly on mitogenic activation. No biochemical or immunological differences were observed between the T cell protein kinase and the previously characterized protein kinase (casein kinase II) from BHK-21 cells. The activity of the kinase that phosphorylates the P protein did not vary in CV-1 cells on treatment with alpha- or gamma-interferon, both of which inhibited VSV replication. Similarly, casein kinase II activities in Raji and SIRC cells, which do not normally support VSV growth, were the same as in BHK-21 cells. Thus restriction of VSV replication in these cells, in contrast to T lymphocytes, was not associated with a deficiency in the host casein kinase II activity.
J Gen Virol 1992 Dec
PMID:Restricted replication of vesicular stomatitis virus in T lymphocytes is coincident with a deficiency in a cellular protein kinase required for viral transcription. 133 23

Incubation of Saccharomyces cerevisiae with the plant cytokinin N6-(delta 2-isopentenyl)adenine (2iP) resulted in an induction of thermotolerance similar to that induced by sublethal temperatures. Intracellular cAMP levels did not change significantly either during incubation at a sublethal temperature or in the presence of 2iP or ethanol. This suggested that stress-induced thermotolerance is triggered by a mechanism independent of cAMP activation. However, measurement of stress-induced thermotolerance in two mutant strains (tpk1, tpk2, TPK3; tpk1, TPK2, tpk3) each deficient in two of the catalytic subunits of the cAMP-dependent protein kinase (cAPK), revealed that sublethal heat induces thermotolerance by a mechanism part-mediated by the catalytic subunits of cAPK. In contrast, 2iP and ethanol induced thermotolerance by a mechanism fully dependent on the catalytic subunits of cAPK for expression. Therefore, this implies there must be an alternative novel mechanism, other than cAMP, for activating cAPK during stress. Sublethal heating resulted in large increases in intracellular trehalose levels which correlated with the induction of thermotolerance. However, incubation in 2iP or ethanol had no significant effect. This suggests trehalose synthesis is either coincidental with heat stress or that different stress factors induce thermotolerance by alternative mechanisms. Incubation with protein synthesis inhibitors reduced the levels of trehalose synthesized during sublethal heating, suggesting that synthesis of trehalose-6-phosphate synthase during heat stress could be accounting for the increased trehalose levels.
J Gen Microbiol 1992 Dec
PMID:TPK gene products mediate cAMP-independent thermotolerance in Saccharomyces cerevisiae. 133 94

Beta-Adrenoceptor agonists activate a time- and voltage-independent Cl- conductance in mammalian cardiac myocytes. To characterize the cellular signaling pathways underlying its regulation, wide-tipped pipettes fitted with a pipette perfusion device were used to record whole-cell current and to introduce nucleotides to the interior of guinea pig ventricular myocytes. Replacement of pipette GTP with GDP beta S prevented activation of the Cl- conductance by Iso, suggesting a requirement for G protein turnover. With GTP in the pipette, the effect of Iso could be abolished by the beta-adrenoceptor antagonist propranolol, and mimicked by histamine or forskolin. These actions of Iso and forskolin are mediated exclusively via cAMP-dependent protein kinase (PKA), because (a) maximal activation of the Cl- conductance by forskolin or pipette cAMP occluded the effect of Iso, and (b) switching to pipette solution containing a synthetic peptide inhibitor (PKI) of PKA completely abolished the Cl- conductance activated by Iso and prevented the action of forskolin, but had no further effect. These results argue against basal activation of the Cl- conductance, and make it extremely unlikely that the stimulatory G protein, Gs, has any direct, phosphorylation-independent influence. The muscarinic receptor agonists acetylcholine (ACh) and carbachol diminished, in a reversible manner, Cl- conductance activated by Iso or forskolin, but not that elicited by cAMP. The muscarinic inhibition was abolished by replacing pipette GTP with GDP beta S, or by preincubating cells with pertussis toxin (PTX), and was therefore mediated by an inhibitory G protein, presumably Gi, influencing adenylyl cyclase activity. Nonhydrolyzable GTP analogues (GTP gamma S or GppNHp) applied via the pipette did not themselves activate Cl- conductance, but rendered Cl- current activation by brief exposures to Iso or histamine, but not to forskolin, irreversible. The Cl- conductance persistently activated by Iso was insensitive to propranolol or ACh, but could still be abolished by pipette application of PKI. The data indicate that stimulation of beta-adrenergic or histaminergic receptors in the presence of nonhydrolyzable GTP analogues causes persistent activation of Gs and uncouples it from the receptors. We conclude that autonomic regulation of cardiac Cl- conductance reflects accurately the underlying modulation of adenylyl cyclase activity and, hence, that this system is a suitable mammalian model for in situ studies of the interactions between adenylyl cyclase, Gs, Gi, and forskolin.
J Gen Physiol 1992 Apr
PMID:Role of GTP-binding proteins in the regulation of mammalian cardiac chloride conductance. 137 58

Using probes obtained by PCR amplification, we have isolated two cognate rice cDNAs (cdc2Os-1 and cdc2Os-2) encoding structural homologues of the cdc2+/CDC28 (cdc2) protein kinase from a cDNA library prepared from cultured rice cells. Comparison of the deduced amino acid sequences of cdc2Os-1 and cdc2Os-2 showed that they are 83% identical. They are 62% identical to CDC28 of Saccharomyces cerevisiae and much more similar to the yeast and mammalian p34cdc2 kinases than to rice R2, a cdc2-related kinase isolated previously by screening the same rice cDNA library with a different oligonucleotide probe. Southern blot analysis indicated that the three rice clones (cdc2Os-1, cdc2Os-2 and R2) are derived from distinct genes and are each found in a single copy per rice haploid genome. RNA blot analysis revealed that these genes are expressed in proliferating rice cells and in young rice seedlings. cdc2Os-1 could complement a temperature-sensitive yeast mutant of cdc28. However, despite the similarity in structure, both cdc2Os-2 and R2 were unable to complement the same mutant. Thus, the present results demonstrate the presence of structurally related, but functionally distinct cognates of the cdc2 cell cycle kinase in rice.
Mol Gen Genet 1992 May
PMID:Isolation and characterization of cDNA clones encoding cdc2 homologues from Oryza sativa: a functional homologue and cognate variants. 137 1

FixL protein of Rhizobium meliloti is a haemo-protein kinase which activates the transcription of nifA and fixK genes via the transcriptional activator protein FixJ under microaerobic conditions. FixL and FixJ proteins belong to the family of two-component regulatory systems for which primary sequence data predicts a modular structure. We showed, using Escherichia coli as heterologous host, that FixL indeed has a modular structure. The amino-terminal hydrophobic domain is dispensable for the oxygen-regulated activity of FixL in vivo. The central cytoplasmic non-conserved domain is necessary for the oxygen-sensing function of FixL whereas it is not necessary for the activation of FixJ by FixL. We propose that, under aerobic conditions, the central domain represses the activating function associated with the carboxy-terminal conserved domain.
Mol Gen Genet 1992 Oct
PMID:Modular structure of the FixL protein of Rhizobium meliloti. 143 30

The DAC2/FUS3 gene of Saccharomyces cerevisiae, which encodes a CDC28/cdc2-related protein kinase, is essential both for the arrest of cell division induced by mating pheromones and for cell fusion during conjugation. To elucidate the role of the DAC2 gene product in the pheromone response pathway, I determined the nucleotide sequence of the DAC2 gene and characterized two types of deletion mutants of the DAC2 gene. Here, I show that the DAC2 gene is identical to the FUS3 gene and that dac2/fus3 deletion mutants respond to mating pheromones by activating transcription. Therefore, the DAC2/FUS3 gene is not essential for transcriptional activation in the pheromone response pathway. The DAC2/FUS3 protein kinase has a positive role in cell fusion during sexual conjugation.
Mol Gen Genet 1992 Nov
PMID:The DAC2/FUS3 protein kinase is not essential for transcriptional activation of the mating pheromone response pathway in Saccharomyces cerevisiae. 146 15

Protein kinases induced by Bombyx mori nuclear polyhedrosis virus in pupae of the silkworm B. mori were examined by activity gel analysis using phosvitin as a protein substrate. The method involved PAGE of the soluble fraction from pupae under native conditions and in the presence of SDS, followed by in situ renaturation of proteins and recovery of protein kinase activity in the intact gel. A novel protein kinase able to phosphorylate phosvitin was detected in the infected pupae from 2 days post-infection. This enzyme was not present in uninfected silkworms at any stage of the pupal period. The novel kinase activity was found by SDS-PAGE to be associated with a single polypeptide with an apparent M(r) of 50K. However, on electrophoresis under native conditions its activity was associated with a set of polypeptides with similar but not identical electrophoretic mobilities. Microheterogeneity of the catalytically active polypeptides suggests that the virus-induced protein kinase undergoes post-translational modification during the course of infection.
J Gen Virol 1992 Dec
PMID:Induction of a novel protein kinase in pupae of the silkworm Bombyx mori after infection with nuclear polyhedrosis virus. 146 62

The yeast gene PBS2 encodes a presumed protein kinase. The gene is essential for manifestation of resistance to the antibiotic polymyxin B. Deletion of PBS2 enables a ras2-530 null mutant to grow on nonfermentable carbon sources; overexpression of PBS2+ enhances viability of a RAS2Val19 mutant. Overexpression of PBS2+ also diminishes cellular response to mating pheromone MF alpha. These results suggest that the PBS2 and RAS2 genes affect a common pathway that may communicate with the pheromone response pathway. In addition, disruption of PBS2 renders cells sensitive to high osmolarity: exposure to 0.9 M-NaCl causes growth arrest, appearance of bizarre morphological forms, and eventual death. A mutation suppressing pbs2 deletion has been found. That mutation restores full polymyxin B resistance but only partially corrects the osmotic sensitivity defect. These observations indicate that PBS2 is involved in diverse physiological pathways in yeast.
J Gen Microbiol 1992 Nov
PMID:PBS2, a yeast gene encoding a putative protein kinase, interacts with the RAS2 pathway and affects osmotic sensitivity of Saccharomyces cerevisiae. 147 60

A new protein kinase gene [called NPK1 (for nonessential protein kinase)] has been found on chromosome I of Saccharomyces cerevisiae between CDC15 and ADE1. The 435 amino acid/48 kDa gene product is very similar to known protein kinases. It is most closely related to the nimA protein of Aspergillus nidulans, displaying 45.9% identity and 63.5% similarity in the protein kinase domain. A 1.4 kb transcript of the NPK1 gene was detected. Disruption of the NPK1 gene impedes neither growth on glucose or a variety of other carbon sources, nor mating or sporulation.
Mol Gen Genet 1992 Jul
PMID:NPK1, a nonessential protein kinase gene in Saccharomyces cerevisiae with similarity to Aspergillus nidulans nimA. 149 80


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