Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Response regulator”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed2003

Beta-lactam resistance modulated by the overexpression of response regulators of two-component signal transduction systems in Escherichia coli.

OBJECTIVES: In Escherichia coli, there are 32 open reading frames assumed, on the basis of sequence similarities, to be response regulator genes of two-component signal transduction systems. We cloned all 32 response regulators and examined whether or not response regulator-overexpressing cells confer resistance to beta-lactam antibiotics in E. coli. METHODS: E. coli KAM3 (acrB), a drug-hypersusceptible mutant, was used as a host strain for the overproduction of response regulators. MICs were determined by the agar dilution method. RESULTS: Thirteen response regulators out of 32 genes, namely baeR, cheY, cpxR, creB, evgA, fimZ, narL, ompR, rcsB, rstA, yedW, yehT and dcuR, conferred increased beta-lactam resistance. Among them, overexpression of baeR, evgA, rcsB and dcuR conferred high-level resistance. The baeR- and evgA-mediated resistance is due to up-regulation of the expression of multidrug exporter genes, acrD and mdtABC for baeR, and yhiUV for evgA, because baeR- and evgA-mediated resistance was completely absent in strains lacking these exporter genes. The fimZ-mediated cefalothin resistance is due to the chromosomal ampC gene, because the ampC deletion strain did not show fimZ-mediated resistance. CONCLUSIONS: Two-component signal transduction systems contribute to beta-lactam resistance in E. coli. Multidrug exporters play roles in two-component signal transduction system-mediated beta-lactam resistance.

Bacterial Proteins↗
PubMed2005

A common docking site for response regulators on the yeast phosphorelay protein YPD1.

In Saccharomyces cerevisiae, a multi-component phosphorelay signal transduction pathway mediates cellular responses to environmental stress. A histidine-containing phosphotransfer protein, YPD1, represents a bifurcation point between the SLN1-YPD1-SSK1 pathway responsible for osmotic stress responses and the SLN1-YPD1-SKN7 pathway involved in cell wall biosynthesis and cell cycle control. The phosphorelay protein YPD1 must physically interact with and transfer phosphoryl groups between three homologous response regulator domains, designated SLN1-R1, SSK1-R2, and SKN7-R3. In this comparative study, the molecular basis of interaction was examined between YPD1 and each of the three response regulator domains utilizing alanine scanning mutagenesis combined with a yeast two-hybrid assay. Results from the yeast two-hybrid assay indicate that all three response regulator domains bind to a common area, largely hydrophobic in nature, on the surface of YPD1. We postulate that other YPD1 surface residues surrounding this common docking site are involved in making specific interactions with one or more of the response regulator domains.

Alanine↗
PubMed2002

Insights into signal transduction revealed by the low resolution structure of the FixJ response regulator.

Two-component regulatory systems mediate most of the bacterial cells responses to a variety of signals. In Sinorhizobium meliloti, the FixL-FixJ couple controls the expression of the nitrogen fixation genes through the binding of the two-domains response regulator FixJ to the fixK and nifA promoters. Phosphorylation of the N-terminal regulatory domain activates the protein and releases the inhibition of the C-terminal DNA-binding domain that occurs in the unphosphorylated protein. Insights into the transition from the inactive to the active form are provided by the architecture of the unphosphorylated response regulator reported in this study. The relative position and orientation of the N and C-terminal domains were defined from the molecular envelope restored from small-angle X-ray scattering (SAXS) data. The involvement of the alpha4-beta5-alpha5 surface of the regulatory domain, the linker region and the C-terminal helix of the DNA-binding domain in the interdomain interface of unphosphorylated FixJ was supported by biochemical investigations. These results, together with the previously reported studies on the phosphorylated regulatory domain of FixJ, emphasize the role of the alpha4-beta5-alpha5 surface in mediating a flow of information in this response regulator. This first study by SAXS of proteins from two-component systems suggests that the method could be successfully applied to other members of this family and could be suitable for the study of multidomain proteins and protein-protein complexes regulated through molecular interfaces in the low micromolar range.

Amino Acid Sequence↗
PubMed2000

Genomic organization and transcriptional regulation of maize ZmRR1 and ZmRR2 encoding cytokinin-inducible response regulators.

Maize genomic clones encoding cytokinin-inducible response regulators, ZmRR1 and ZmRR2, have been isolated. In comparison with the corresponding cDNAs, ZmRR2 was found to be interrupted in the translated region by an intron whereas ZmRR1 was not. The 5'-flanking regions of the two genes shared conserved regions and putative cis-elements, which had been identified in maize or other plant species. The run-on transcription assay and the analysis of stable maize transformants of ZmRR1 promoter-beta-glucuronidase fusion gene revealed that the accumulation of the transcripts in response to cytokinins is, at least in parts, attributed by transcriptional activation.

Cytokinins↗
PubMed1985

Cue significance and response regulation in 3- to 6-year-old children's learning of multiple choice discrimination tasks.

The learning of multiple choice discrimination tasks of 3-, 4-, 5-, and 6-year-old children was compared using the components of learning of cue significance and response regulation. No significant differences between age groups were found in the occurrence of cue significance learning, although the younger children's cue significance responses were less accurately related to task solution. On the two easier tasks, the component of response regulation improved significantly over the age range of 3-5 years. On the two more difficult tasks 6-year-olds' response regulation was significantly better than that of 4- and 5-year-olds. In a second experiment involving two different training procedures, 5-year-olds performed better than 4-year-olds. Only for 5-year-olds was performance with the procedure emphasizing response regulation superior to performance with the procedure emphasizing cue significance. These results are discussed in terms of an association between development of response regulation and maturation of hippocampal-prefrontal cortex systems.

Child↗
PubMed2006

Modulation of Mycobacterium tuberculosis proliferation by MtrA, an essential two-component response regulator.

Paired two-component regulatory systems consisting of a sensor kinase and a response regulator are the major means by which bacteria sense and respond to different stimuli. The role of essential response regulator, MtrA, in Mycobacterium tuberculosis proliferation is unknown. We showed that elevating the intracellular levels of MtrA prevented M. tuberculosis from multiplying in macrophages, mice lungs and spleens, but did not affect its growth in broth. Intracellular trafficking analysis revealed that a vast majority of MtrA overproducing merodiploids were associated with lysosomal associated membrane protein (LAMP-1) positive vacuoles, indicating that intracellular growth attenuation is, in part, due to an impaired ability to block phagosome-lysosome fusion. A merodiploid strain producing elevated levels of phosphorylation-defective MtrA (MtrA(D53N)) was partially replicative in macrophages, but was attenuated in mice. Quantitative real-time PCR analyses revealed that expression of dnaA, an essential replication gene, was sharply upregulated during intramacrophage growth in the MtrA overproducer in a phosphorylation-dependent manner. Chromatin immunoprecipitation using anti-MtrA antibodies provided direct evidence that MtrA regulator binds to dnaA promoter in vivo indicating that dnaA promoter is a MtrA target. Simultaneous overexpression of mtrA regulator and its cognate mtrB kinase neither inhibited growth nor sharply increased the expression levels of dnaA in macrophages. We propose that proliferation of M. tuberculosis in vivo depends, in part, on the optimal ratio of phosphorylated to non-phosphorylated MtrA response regulator.

ATP-Binding Cassette Transporters↗
PubMed2004

A regulation cascade controls expression of Porphyromonas gingivalis fimbriae via the FimR response regulator.

Little is known about how Porphyromonas gingivalis, a Gram-negative oral anaerobe, senses environmental changes, and how such information is transmitted to the cell. The production of P. gingivalis surface fimbriae is regulated by FimS-FimR, a two component signal transduction system. Expression of fimA, encoding the fimbrilin protein subunit of fimbriae, is positively regulated by the FimR response regulator. In this study we investigated the molecular mechanisms of FimR regulation of fimA expression. Comparative transcription profiling of fimR wild-type and mutant strains shows that FimR controls the expression of several genes including five clustered around the fimA locus. Chromatin immunoprecipitation assays and electrophoretic mobility shift assays identify and confirm that FimR binds to the promoter region of the first gene in the fimA cluster. Gene expression analyses of mutant strains reveal a transcriptional cascade involving multiple steps, with FimR activating expression of the first gene of the cluster that encodes a key regulatory protein.

Animals↗
PubMed2003

Structural analysis of the domain interface in DrrB, a response regulator of the OmpR/PhoB subfamily.

The N-terminal regulatory domains of bacterial response regulator proteins catalyze phosphoryl transfer and function as phosphorylation-dependent regulatory switches to control the output activities of C-terminal effector domains. Structures of numerous isolated regulatory and effector domains have been determined. However, a detailed understanding of regulatory interactions among these domains has been limited by the relative paucity of structural data for intact multidomain response regulator proteins. The first multidomain structures determined, those of transcription factor NarL and methylesterase CheB, both revealed extensive interdomain interfaces. The regulatory domains obstruct access to the functional sites of the effector domains, indicating a regulatory mechanism based on inhibition. In contrast, the recently determined structure of the OmpR/PhoB homologue DrrD revealed no significant interdomain interface, suggesting that the domains are tethered by a flexible linker and lack a fixed orientation relative to each other. To address the generality of this feature, we have determined the 1.8-A resolution crystal structure of Thermotoga maritima DrrB, providing a second structure of a multidomain response regulator of the OmpR/PhoB subfamily. The structure reveals an extensive domain interface of 751 A(2) and therefore differs greatly from that observed in DrrD. Residues that are crucial players in defining the activation state of the regulatory domain contribute to this interface, implying that conformational changes associated with phosphorylation will influence these intramolecular contacts. The DrrB and DrrD structures are suggestive of different signaling mechanisms, with intramolecular communication between N- and C-terminal domains making substantially different contributions to effector domain regulation in individual members of the OmpR/PhoB family.

Bacterial Proteins↗
PubMed2002

His-Asp phosphorelay signal transduction in higher plants: receptors and response regulators for cytokinin signaling in Arabidopsis thaliana.

Bacteria have devised phosphotransfer signaling mechanisms for eliciting a variety of adaptive responses to their environment. These mechanisms are collectively referred to as two-component regulatory systems. Each system generally consists of a sensor protein histidine kinase, which is anchored in the cell membrane, and a cytoplasmic response regulator, whose activity is modulated by the sensor. Most response regulators are transcription factors. In this review, we briefly introduce the established concept on bacterial two-component regulatory systems, using the Agrobacterium VirA-VirG system as an example, and give the evidence for the existence of quite similar systems in higher plants, such as the signal transduction induced by the phytohormone cytokinin. The Arabidopsis CRE1 histidine kinase and its related proteins AHK2 and AHK3 perceive cytokinins in the environment and transduce a signal, presumably through the AHP bridge components that carry the histidine-containing phosphotransfer (HPt) domain, to the ARR1 response regulator that transcriptionally activates genes immediately responsive to cytokinins. In addition, this signal transfer process appears to participate in cross-talk with signaling systems that respond to daylight and another phytohormone, ethylene, through an intracellular pool of several ARR1-like molecular species and the AHP components.

Arabidopsis↗
PubMed2005

Primary and secondary modes of DNA recognition by the NarL two-component response regulator.

NarL is a model response regulator for bacterial two-component signal transduction. The NarL C-terminal domain DNA binding domain alone (NarL(C)) contains all essential DNA binding determinants of the full-length NarL transcription factor. In the full-length NarL protein, the N-terminal regulatory domain must be phosphorylated to release the DNA binding determinants; however, the first NarL(C)-DNA cocrystal structure showed that dimerization of NarL(C) on DNA occurs in a manner independent of the regulatory domain [Maris, A. E., et al. (2002) Nat. Struct. Biol. 9, 771-778]. Dimerization via the NarL(C) C-terminal helix conferred high-affinity recognition of the tail-to-tail promoter site arrangement. Here, two new cocrystal structures are presented of NarL(C) complexed with additional 20mer oligonucleotides representative of other high-affinity tail-to-tail NarL binding sites found in upstream promoter regions. DNA structural recognition properties are described, such as backbone flexibility and groove width, that facilitate NarL(C) dimerization and high-affinity recognition. Lys 188 on the recognition helix accommodates DNA sequence variation between the three different cocomplexes by providing flexible specificity, recognizing the DNA major groove floor directly and/or via bridging waters. The highly conserved Val 189, which enforced significant DNA base distortion in the first cocrystal structure, enforces similar distortions in the two new cocrystal structures. Recognition also is conserved for Lys 192, which hydrogen bonds to guanines at regions of high DNA helical writhe. DNA affinity measurements for model NarL binding sites, including those that did not cocrystallize, suggest a framework for explaining the diversity of heptamer site arrangement and orientation.

Amino Acid Sequence↗
PubMed1999

Activation of the cycA P2 promoter for the Rhodobacter sphaeroides cytochrome c2 gene by the photosynthesis response regulator.

The Rhodobacter sphaeroides photosynthesis response regulator, PrrA, positively regulates cycA P2 expression. Deletion analysis has identified sequences within 73 bp upstream of the transcription initiation site that are required for the activation of cycA P2 by PrrA. A mutant form of the Rhodobacter capsulatus PrrA homologue, whose activity is independent of phosphorylation (RegA*), protects an approximately 26 bp region of cycA P2 that is centred at approximately -50 from DNase digestion, and activates transcription of a mutant -14T promoter with increased activity when using either R. sphaeroides RNA polymerase or Escherichia coli Esigma70. A 4 bp target site mutation that eliminated DNA binding and transcription activation by RegA* in vitro also abolished PrrA activation of cycA P2 transcription in vivo, indicating that this region contains a PrrA binding site. By analysing the behaviour of the -14T mutant cycA P2 promoter in vivo, we also found that PrrA uses the same target site to activate expression in both the presence and the absence of O2. However, the extent of transcription activation by PrrA at cycA P2 in vivo is greater under anaerobic conditions.

Bacterial Proteins↗
PubMed1999

Crystallization of the regulatory and effector domains of the key sporulation response regulator Spo0A.

The key response-regulator gene of sporulation, spo0A, has been cloned from Bacillus stearothermophilus and the encoded protein purified. The DNA-binding and phospho-acceptor domains of Spo0A have been prepared by tryptic digestion of the intact protein and subsequently crystallized in forms suitable for X-ray crystallographic studies. The DNA-binding domain has been crystallized in two forms, one of which diffracts X-rays to beyond 2. 5 A spacing. The crystals of the phospho-acceptor domain diffract X-rays beyond 2.0 A spacing using synchrotron radiation.

Amino Acid Sequence↗
PubMed1995

A common switch in activation of the response regulators NtrC and PhoB: phosphorylation induces dimerization of the receiver modules.

During signal transduction, response regulators of two-component systems are phosphorylated in a conserved receiver module. Phosphorylation induces activation of the non-conserved output domain. We fused various domains of the response regulators NtrC, PhoB or CheB to the DNA binding domain of lambda repressor. Analysis of these hybrid proteins shows that the receiver modules of NtrC and PhoB are potential dimerization domains. In the unphosphorylated proteins, the ability of the receiver modules to dimerize is masked due to inhibition by their output domains. Inhibition can be relieved in two ways: phosphorylation of the receiver module or deletion of the output domain. In contrast, the receiver module of CheB lacks this ability for dimerization. We propose a model which groups response regulators into two classes. Common to both classes is the interaction between receiver and output domain in the unphosphorylated protein. In class I (e.g. NtrC and PhoB), this interaction leads to the inhibition of the receiver module. Phosphorylation relieves inhibition, thereby inducing activation via dimerization of the receiver modules. In class II (e.g. CheB), the interaction between receiver and output domain results in inhibition of the output domain. Phosphorylation relieves inhibition, thereby activating the output domain.

Adenosine Triphosphatases↗
PubMed1993

Dual response regulators (NarL and NarP) interact with dual sensors (NarX and NarQ) to control nitrate- and nitrite-regulated gene expression in Escherichia coli K-12.

Two sensor proteins, NarX and NarQ, mediate nitrate regulation of anaerobic respiratory gene expression. Either of these sensors is sufficient to signal the presence of nitrate to the response regulator protein, NarL, a transcriptional activator and repressor. Two observations suggested the existence of a second response regulator that is also involved in nitrate regulation. First, narL null mutants retain residual nitrate induction of fdnG operon expression; this residual induction is absent in narX narQ double-null strains. Second, nitrate induction of aeg-46.5 operon expression is substantially enhanced in narL null strains (M.H. Choe and W.S. Reznikoff, J. Bacteriol. 173:6139-6146, 1991). We found that this nitrate induction requires either the NarX or the NarQ protein, consistent with the existence of a second response regulator. We designate this second regulator NarP. We isolated insertion mutants that are defective in aeg-46.5 operon expression. These insertions are in the narP gene, which encodes a response regulator that is 44% identical to the NarL protein. Null alleles of narP abolished aeg-46.5 induction and also eliminated the residual NarL-independent nitrate induction of fdnG operon expression. Both the NarX and NarQ proteins communicate with both the NarP and NarL proteins. We found that the primary signal for NarP-dependent aeg-46.5 operon induction is nitrite rather than nitrate. By contrast, nitrite is a relatively weak signal for NarL-dependent induction. In narX null strains, nitrate was an efficient signal for NarL-dependent induction, and this induction required the NarQ protein. We conclude that, in wild-type strains, the NarQ protein communicates the presence of nitrite to both the NarP and NarL proteins and that the NarX protein inhibits this communication with the NarL protein.

Amino Acid Sequence↗
PubMed2000

The pleiotropic response regulator DegU functions as a priming protein in competence development in Bacillus subtilis.

The response regulator DegU is involved in various late-growth developmental processes in Bacillus subtilis, including the production of degradative enzymes and the development of genetic competence. DegU is essential for the expression of the competence transcription factor, encoded by comK. ComK is required for the transcription of genes encoding the DNA uptake and integration machinery, as well as for the transcription of its own gene. We have purified DegU to study its role in the expression of comK, and we demonstrate here that DegU binds specifically to the comK promoter. The binding of the response regulator DegU to a promoter target had not been reported previously. DNase I protection analyses show that the DegU binding site overlaps with the ComK binding site, and gel retardation experiments indicate that DegU strongly stimulates the binding of ComK to the comK promoter. We propose that DegU functions at the initiation of competence development, when ComK concentrations are insufficient to support comK transcription, by facilitating ComK binding to the comK promoter. DegU therefore acts as a priming protein that primes the autostimulatory transcription of comK. Such priming activity adds a function to the class of response regulator proteins.

Bacillus subtilis↗
PubMed1996

Aspartyl-phosphate phosphatases deactivate the response regulator components of the sporulation signal transduction system in Bacillus subtilis.

Bacteria use two-component signal transduction systems to sense and respond to their environment. A sensor kinase and a response-regulator transcription factor work in concert by phosphorylation/dephosphorylation through kinase and phosphatase activities to maintain a level of phosphorylated response regulator commensurate with the level of signal input. Signal input can be accommodated through stimulation of the kinase activity or the phosphatase activity of the two-component system. With some notable exceptions, the sensor kinases recognize a single stimulatory ligand. A new dimension in the regulation of two-component signal transduction systems was discovered in the Rap phosphatases which dephosphorylate the SpoOF response-regulator of Bacillus subtilis independent of the sensor kinases. This family of phosphatases is encoded by at least six chromosomal genes. Although not all of the phosphatases of the family have activity on phosphorylated SpoOF, the two best-characterized members, RapA and RapB, prevent sporulation by dephosphorylating this response regulator component of the phosphorelay. Phosphatase activity of RapA is regulated by a gene, phrA, in the same transcriptional unit, that encodes a peptide secreted from the cell which may serve as a quorum sensor. Most of the Rap phosphatase operons have a gene coding for a protein with some similarity to PhrA in their transcription units, but it is uncertain whether all of these play a role in regulation. The Rap phosphatases are postulated to be a mechanism for allowing signals other than those that affect the sensor kinases to regulate the signal transduction pathway. They may have been recruited to help regulate sporulation because the multiple signals regulating this process may outstrip the recognition capacity of the kinases.

ATP-Binding Cassette Transporters↗
PubMed2001

The response regulator ARR2: a pollen-specific transcription factor involved in the expression of nuclear genes for components of mitochondrial complex I in Arabidopsis.

Two-component signal systems regulate a variety of cellular activities. They involve at least two common signalling molecules: a signal-sensing kinase and a response regulator that mediates the output response. Multistep systems also require proteins containing phosphotransfer domains. Here we report that the response regulator ARR2 from Arabidopsis is predominantly expressed in pollen and is localized in the nuclear compartment of the plant cell. Furthermore, ARR2 is transcriptionally active in yeast and binds to the promoters of nuclear genes for several components of mitochondrial respiratory chain complex I (nCI) from Arabidopsis. The nuclear nCI genes are up-regulated in pollen during spermatogenesis. The transcription factor functions of ARR2 are mediated by its C-terminal output domain. Our data identify ARR2 as the first eukaryotic response regulator which functions as a transcription factor at a known promoter sequence. Yeast two-hybrid analysis and in vitro interaction studies suggest that ARR2 very probably forms part of a multistep two-component signalling mechanism that includes HPt proteins like AHP1 or AHP2. These findings point to an as yet unidentified signal transduction system that may regulate aspects of floral and mitochondrial gene expression.

Arabidopsis↗
PubMed1999

Identification of a putative response regulator two-component phosphorelay gene ( CaSSK1) from Candida albicans.

We have identified and analysed a putative response regulator two-component gene (CaSSK1) from Candida albicans and its encoding protein (CaSsk1p). CaSSK1 has an open reading frame of 2022 bp. In the promotor region of CaSSK1 a short sequence is found that matches the consensus sequence of the stress response elements (STRE) from Saccharomyces cerevisiae. CaSSK1 is located on chromosome 1 and is expressed in either yeast or mycelial phases of C. albicans. CaSSK1 encodes a 674 amino acid protein (CaSsk1p) with an estimated molecular mass of 73.5 kDa and a basic isoelectric point (pI 9.5). It has a tripeptide (NKA) located in its C-terminus, which resembles the peroxisomal signalling target type 1 sequence (PST1) of most of the peroxisomal matrix proteins. A homology search of CaSsk1p with other proteins in databases showed that the C-terminus of CaSsk1p exhibits the greatest similarity with the C-terminus of Ssk1p and Mcs4 from Saccharomyces cerevisiae and Schizosaccharomyces pombe, respectively. The response regulator domain of CaSsk1p contains the motifs that are characteristic of all response regulators, including the conserved aspartate and lysine residues as well as the putative aspartate, which is phosphorylated by a phosphohistidine residue. Finally, in spite of the structural similarities among CaSsk1p, Ssk1p and Mcs4, CaSsk1p does not seem to exhibit functional homology with these proteins.

Amino Acid Sequence↗