Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.13.3 (histidine kinase)
 2,405 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A wide variety of mechanisms have evolved for intercellular communication in metazoans, but some of the signaling molecules were already used in their predecessors. The social amoeba, Dictyostelium discoideum, is known to use peptides to trigger sporulation within fruiting bodies, but their sequences have not been defined. We found that the peptide signal spore differentiation factor 2 (SDF-2) is processed from acyl-CoA binding protein, AcbA. The mammalian homolog of AcbA is processed to diazepam binding inhibitor that binds to the GABA(A) receptor in the brain and to peripheral 1,4 benzodiazepine receptors. Although Dictyostelium has neither GABA(A) nor peripheral-type benzodiazepine receptors, we find that both a diazepam binding inhibitor peptide and diazepam (Valium) can mimic SDF-2 in a Dictyostelium bioassay. Mutants lacking AcbA sporulate well only when developed in chimeras with WT cells. Using a yeast system we show that ligand binding to the SDF-2 receptor histidine kinase, DhkA, inhibits phosphorelay, which can account for its ability to induce rapid sporulation.
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PMID:Peptide signaling during terminal differentiation of Dictyostelium. 1589 58

Identifying the direct target genes of response regulators (RRs) of a bacterial two-component system (TCS) is critical to understand the roles of TCS in bacterial environmental adaption and pathogenesis. Actinobacillus pleuropneumoniae is an important respiratory bacterial pathogen that causes considerable economic losses to swine industry worldwide. The targets of A. pleuropneumoniae NarP (nitrate/nitrite RR), which is the cognate RR of the nitrate/nitrite sensor histidine kinase NarQ, are still unknown. In the present study, a DNA-affinity-purified sequencing (DAP-Seq) approach was established. The upstream regions of a total of 131 candidate genes from the genome of A. pleuropneumoniae were co-purified with the activated NarP protein. Electrophoretic mobility shift assay (EMSA) results confirmed the interactions of NarP with the promoter regions of five selected target genes, including dmsA, pgaA, ftpA, cstA and ushA. The EMSA-confirmed target genes were significantly up-regulated in the narP-deleted mutant in the presence of additional nitrate, whilst the transcriptional changes were restored in the complemented strain. The NarP binding motif in the upstream regions of the target genes dmsA and ftpA were further identified and confirmed by EMSA using the truncated binding motif. The NarP binding sites were present in a total of 25.2% of the DNA fragments captured by DAP-Seq. These results demonstrated that the established DAP-Seq method is effective for exploring the direct targets of RRs of bacterial TCSs and that the A. pleuropneumoniae NarP could be a repressor in response to nitrate.
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PMID:Identification of genes regulated by the two-component system response regulator NarP of Actinobacillus pleuropneumoniae via DNA-affinity-purified sequencing. 3153 52