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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The yeast histidine kinase, Sln1p, is a plasma membrane-associated osmosensor that regulates the activity of the osmotic stress MAP kinase pathway. Changes in the osmotic environment of the cell influence the autokinase activity of the cytoplasmic kinase domain of Sln1p. Neither the nature of the stimulus, the mechanism by which the osmotic signal is transduced nor the manner in which the kinase is regulated is currently clear. We have identified several mutations located in the linker region of the Sln1 kinase (just upstream of the kinase domain) that cause hyperactivity of the Sln1 kinase. This region of histidine kinases is largely uncharacterized, but its location between the transmembrane domains and the cytoplasmic kinase domain suggests that it may have a potential role in signal transduction. In this study, we have investigated the Sln1 linker region in order to understand its function in signal transduction and regulation of Sln1 kinase activity. Our results indicate that the linker region forms a coiled-coil structure and suggest a mechanism by which alterations induced by osmotic stress influence kinase activity by altering the alignment of the phospho-accepting histidine with respect to the catalytic domain of the kinase.
Mol Microbiol 2002 Jan
PMID:A cytoplasmic coiled-coil domain is required for histidine kinase activity of the yeast osmosensor, SLN1. 1198 22

Interleukin-8 (Il-8) and IL-10 are cytokines associated with the Epstein Barr Virus (EBV), which is linked with nasopharyngeal cancer (NPC). In the present study, we investigated the endogenous production of IL-8 and IL-10 in vitro by two EBV-positive NPC cell lines, viz., HK1 and CNE-2. IL-8 was expressed by both cell lines although the level of IL-8 was 2-fold higher in supernatant from HK1 cells. Incubation with hypericin, a natural photosensitizer increased IL-8 significantly but only in HK1 cells. Hypericin-based photodynamic therapy (PDT) did not alter the expression of IL-8 levels. Il-10 was not constitutively expressed in either cell line and could not be induced by PDT. It is interesting that PDT which is known to upregulate IL-8 transcription via reactive oxygen species and activate the IL-10 promoter did not alter IL-8 levels in either of the NPC cell lines nor induced the production of IL-10.
Int J Mol Med 2002 Jul
PMID:Endogenous expression of interleukin-8 and interleukin-10 in nasopharyngeal carcinoma cells and the effect of photodynamic therapy. 1206 Aug 53

Spo0A~P is the essential response regulator and transcription factor for sporulation initiation in Bacillus subtilis. The phosphorylation level of Spo0A in the cell is determined by the sensor kinase activity of the phosphorelay, donating phosphoryl groups, and the antagonistic effects of dephosphorylation mediated by the Rap and Spo0E families of phosphatases. In this study, spo0A mutations were generated that encoded proteins less sensitive to the activity of Spo0E than the wild-type protein. The Spo0A substitutions N12K, P60S, L62P and F88L are surface exposed and localize to the same face of the molecule as the active site and in its close proximity on the beta1-alpha1, beta3-alpha3 and beta4-alpha4 loops. The corresponding surface in the Spo0F response regulator was shown previously to be involved in the interaction with the RapB phosphatase, as well as the KinA histidine kinase and the Spo0B phosphotransferase. Thus, residues occupying the same position (N12:Q12, F88:Y84) and the same loops in Spo0A or Spo0F are involved in the interaction with the structurally unrelated Spo0E and RapB phosphatases, respectively, in addition to kinases and phosphotransferase. The specificity in phosphatase target recognition must be the result of side-chain variability within the response regulators and the interactions they promote. The residues involved in Spo0E interaction are identical in all Spo0A orthologues from spore-forming Bacilli encoding Spo0E phosphatases.
Mol Microbiol 2002 Jun
PMID:Interaction surface of the Spo0A response regulator with the Spo0E phosphatase. 1206 36

Salmonella enterica serovar Typhimurium periodically experiences acid stress in a variety of host and non-host environments. An encounter with non-lethal acid stress (pH > 4) induces an assortment of physiological changes, called the acid tolerance response (ATR), that helps the cell to tolerate extreme low pH (pH 3). These physiological changes differ in log phase and stationary phase cells and are controlled by different regulatory proteins. OmpR is an acid-induced response regulator critical to the stationary phase ATR but not to the log phase ATR. As OmpR also controls the expression of the acid-induced virulence operon ssrAB, acid shock induction of ompR was examined to gain insight into how Salmonella links virulence with survival at extreme acid pH. The results indicate that acid pH induces ompR from a promoter different from that used for basal expression. Transcription from this promoter is repressed by the histone-like protein H-NS and requires OmpR-P for induction. The classic sensor kinase EnvZ and acetyl phosphate collaborate to produce the optimum level of OmpR-P needed for autoinduction. Although OmpR-P is required for acid-induced expression of ompR in wild-type cells, OmpR is not needed for ompR transcription in the absence of H-NS. Thus, the role of OmpR-P in autoinduction is to help to counteract repression by H-NS. This evidence, combined with the finding that relaxing DNA supercoiling with novobiocin also increased ompR transcription, suggests that acid stress induces ompR by altering local DNA topology, not by changing the phosphorylation status of OmpR.
Mol Microbiol 2002 Jun
PMID:Autoinduction of the ompR response regulator by acid shock and control of the Salmonella enterica acid tolerance response. 1206 8

The 90-kDa heat shock family (HSP90) of protein and two-component histidine kinases, although quite distinct at the primary amino acid sequence level, share a common structural ATP-binding domain known as the Bergerat fold. The Bergerat fold is important for the ATPase activity and associated chaperone function of HSP90. Two-component histidine kinases occur in bacteria, yeast, and plants but have yet to be identified in mammalian cells. The antifungal antibiotic radicicol (Monorden) has been shown to bind to the Bergerat fold of HSP90 and to inhibit its ATPase activity. The structural similarity between the Bergerat fold of HSP90 and bacterial two-component histidine kinases prompted our inquiry into whether radicicol could be a potential inhibitor of histidine kinase-like proteins. Structural homology searches suggest that the ATP-binding domains of the yeast histidine kinase Sln1 and the mammalian, branched-chain alpha-keto acid dehydrogenase kinase are very similar to that of other Bergerat fold family members. On the basis of structural homology, we tested radicicol as a potential inhibitor of Sln1 and branched-chain alpha-keto acid dehydrogenase kinase (BCKDHK) and propose a mechanism of inhibition of these kinases. Although BCKDHK has been shown to have serine autophosphorylation activity, we speculate, based on the results from this study and other supporting evidence, that BCKDHK may also have intrinsic histidine kinase activity.
Mol Pharmacol 2002 Aug
PMID:Inhibition of branched-chain alpha-keto acid dehydrogenase kinase and Sln1 yeast histidine kinase by the antifungal antibiotic radicicol. 1213 Jun 80

Histidine kinase EnvZ, a transmembrane osmotic sensor for Escherichia coli, is a bifunctional enzyme having OmpR (its cognate response regulator) kinase and phosphorylated OmpR (OmpR-P) phosphatase activities. Its cytoplasmic domain consists of domain A responsible for dimerization of EnvZ, histidine phosphotransfer and phosphatase activities, and domain B responsible for ATP binding. Here, we have constructed a number of substitution mutations at the G2 box, one of the conserved motifs in domain B, and demonstrated that they influence the phosphatase activity of EnvZ over a wide range. The effects of ADP, a cofactor for the phosphatase activity, were found to be substantially different depending upon the mutations. The effects of these mutations were also examined in vivo using a chimeric Tar-EnvZ construct (Taz1-1), and the results agreed with the in vitro data for the phosphatase and kinase activities for all mutations. Using Taz1-1 carrying the T402A mutation, three independent intragenic suppressor mutations (T235M, S269L and E276K) were isolated, and all were found in domain A. Together, the present results demonstrate for the first time that domain A and domain B are functionally co-ordinated and topologically arranged in a specific manner. The G2 box may modulate the interaction between these two domains in response to extracellular osmolarity.
Mol Microbiol 2002 Aug
PMID:The role of the G2 box, a conserved motif in the histidine kinase superfamily, in modulating the function of EnvZ. 1213 13

We have systematically examined the mRNA profiles of 36 two-component deletion mutants, which include all two-component regulatory systems of Escherichia coli, under a single growth condition. DNA microarray results revealed that the mutants belong to one of three groups based on their gene expression profiles in Luria-Bertani broth under aerobic conditions: (i) those with no or little change; (ii) those with significant changes; and (iii) those with drastic changes. Under these conditions, the anaeroresponsive ArcB/ArcA system, the osmoresponsive EnvZ/OmpR system and the response regulator UvrY showed the most drastic changes. Cellular functions such as flagellar synthesis and expression of the RpoS regulon were affected by multiple two-component systems. A high correlation coefficient of expression profile was found between several two-component mutants. Together, these results support the view that a network of functional interactions, such as cross-regulation, exists between different two-component systems. The compiled data are avail-able at our website (http://ecoli.aist-nara.ac.jp/xp_analysis/ 2_components).
Mol Microbiol 2002 Oct
PMID:Transcriptome analysis of all two-component regulatory system mutants of Escherichia coli K-12. 1236 50

The stress imposed on living organisms by hyperosmotic conditions and low temperature appears to be perceived via changes in the physical state of membrane lipids. We compared genome-wide patterns of transcription between wild-type Synechocystis sp. PCC 6803 and cells with a mutation in the histidine kinase Hik33 using a DNA microarray. Our results indicated that Hik33 regulated the expression of both osmostress-inducible and cold-inducible genes. The respective genes that were regulated by Hik33 under hyperosmotic and low-temperature conditions were, for the most part, different from one another. However, Hik33 also regulated the expression of a set of genes whose expression was induced both by osmotic stress and by cold stress. These results indicate that Hik33 is involved in responses to osmotic stress and low-temperature stress but that the mechanisms of the responses differ.
Mol Microbiol 2002 Nov
PMID:The histidine kinase Hik33 perceives osmotic stress and cold stress in Synechocystis sp PCC 6803. 1242 Dec 99

EnvZ, a histidine kinase, and its cognate response regulator OmpR of Escherichia coli are responsible for adaptation to external osmotic changes by regulating the levels of the outer membrane porin proteins, OmpF and OmpC. The osmosensor, EnvZ, has dual enzymatic functions with OmpR kinase and OmpR-P phosphatase. Here, we demonstrate that the cytoplasmic kinase domain of EnvZ (EnvZc) and OmpR are able to form a 1:1 complex detected by native PAGE. This indicates that two OmpR molecules can bind to one EnvZc dimer. As this 1:1 EnvZc/OmpR complex is formed even in the presence of a large excess of EnvZc, OmpR binding to EnvZc is co-operative. The complex formation is also observed between EnvZc and phosphorylated OmpR for the phosphatase reaction. OmpR-P bound to EnvZc was readily released upon the addition of OmpR, indicating that OmpR and OmpR-P can compete for the binding to EnvZ. On the basis of these results, a model is discussed to explain how cellular OmpR-P concentrations are regulated in response to medium osmolarity.
Mol Microbiol 2002 Dec
PMID:Formation of the stoichiometric complex of EnvZ, a histidine kinase, with its response regulator, OmpR. 1245 14

EnvZ is a sensory histidine kinase in Escherichia coli to regulate the phosphorylation of OmpR, its cognate response regulator, required for the expression of genes for outer membrane porin proteins. Here, we re-examined the recent paper Mattison and Kenney, in which the authors reported that phosphorylated OmpR (OmpR-P) is unable to bind to EnvZ, thus casting doubts on the role of the EnvZ phosphatase activity in vivo. Using an identical method, the Kd value for the interaction of the fluorescein-labelled OmpR (Fl-OmpR) with EnvZc was determined to be 1.96 +/- 0.28 micro M. We demonstrated that OmpR-P as well as OmpR inhibited the interaction of Fl-OmpR with EnvZc. Their 50% inhibitory concentrations were 1.09 +/- 0.25 micro M and 0.89 +/- 0.14 micro M, respectively, under the conditions used. The interaction between His-10-OmpR and EnvZc was also inhibited almost equally with OmpR-P and OmpR. Fluorescein labelling of OmpR was highly heterogeneous as detected by mass spectrometry, even though it slightly affected the OmpR phosphorylation (kinase) and the dephosphorylation of OmpR-P (phosphatase), indicating that EnvZc is able to interact with Fl-OmpR or Fl-OmpR-P as well as with OmpR or OmpR-P as a substrate. We demonstrated that OmpR-P is able to interact with EnvZc with a similar affinity to OmpR and serves as an effective substrate for the EnvZ phosphatase. These findings support the hypothesis that osmotic signals regulate the level of the cellular concentration of OmpR-P by modulating the ratio of kinase to phosphatase activity of the bifunctional enzymatic activities of EnvZ.
Mol Microbiol 2002 Dec
PMID:Interaction of EnvZ, a sensory histidine kinase, with phosphorylated OmpR, the cognate response regulator. 1245 15


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