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)

Ly-6C is a differentiation antigen that distinguishes T-lymphocyte subsets. In concordance with previous results, splenocytes from NOD mice do not express the epitope recognized by anti-Ly-6C monoclonal antibodies (MoAbs), including MoAb HK1.4 in this study, and cannot be stimulated to proliferate in response to HK1.4. However, when splenocytes from NOD mice were stimulated in vitro with the anti-CD3 MoAb 145-2C11, T lymphocytes expressing Ly-6C were detected after 48 h of stimulation, with as many as 25% of lymphocytes expressing this antigen with prolonged passage in culture. Most of the cells expressing Ly-6C were Thy-1.2+, CD4+, and CD8- and proliferated after stimulation with HK1.4. To further understand the failure of NOD splenocytes to express Ly-6C, freshly isolated cells were stimulated with alpha/beta-interferon (IFN-alpha/beta) and IFN-gamma. Although these lymphokines induced expression of Ly-6A and Ly-6C in splenocytes from C57BL/6J mice and Ly-6A in NOD cells, Ly-6C was not induced on NOD cells. Because Ly-6C expression on splenocytes was a marker of activation via the CD3 T-lymphocyte receptor complex, we also examined expression of Ly-6C on T lymphocytes within islets showing insulitis in vivo. Lymphocytes that were Ly-6C+ were identified within islets on histological sections of pancreas, whereas Ly-6C+ cells in the spleen from the same mouse could not be detected. Our findings imply functional abnormality in expression of Ly-6C in NOD mice.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of Ly-6C by T lymphocytes of NOD mice after CD3-complex stimulation. Identification of activated cells during insulitis of prediabetic mice. 216 2

The exoproteome of Staphylococcus aureus contains enzymes and virulence factors that are important for host adaptation. We investigated the exoprotein profiles and cytokine/chemokine responses obtained in three different S. aureus-host interaction scenarios by using two-dimensional gel electrophoresis (2-DGE) and two-dimensional immunoblotting (2D-IB) combined with tandem mass spectrometry (MS/MS) and cytometric bead array techniques. The scenarios included S. aureus bacteremia, skin and soft tissue infections (SSTIs), and healthy carriage. By the 2-DGE approach, 12 exoproteins (the chaperone protein DnaK, a phosphoglycerate kinase [Pgk], the chaperone GroEL, a multisensor hybrid histidine kinase, a 3-methyl-2-oxobutanoate hydroxymethyltransferase [PanB], cysteine synthase A, an N-acetyltransferase, four isoforms of elongation factor Tu [EF-Tu], and one signature protein spot that could not be reliably identified by MS/MS) were found to be consistently present in more than 50% of the bacteremia isolates, while none of the SSTI or healthy-carrier isolates showed any of these proteins. By the 2D-IB approach, we also identified five antigens (methionine aminopeptidase [MetAPs], exotoxin 15 [Set15], a peptidoglycan hydrolase [LytM], an alkyl hydroperoxide reductase [AhpC], and a haptoglobin-binding heme uptake protein [HarA]) specific for SSTI cases. Cytokine and chemokine production varied during the course of different infection types and carriage. Monokine induced by gamma interferon (MIG) was more highly stimulated in bacteremia patients than in SSTI patients and healthy carriers, especially during the acute phase of infection. MIG could therefore be further explored as a potential biomarker of bacteremia. In conclusion, 12 exoproteins from bacteremia isolates, MIG production, and five antigenic proteins identified during SSTIs should be further investigated for potential use as diagnostic markers.
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PMID:Comparative Exoproteomics and Host Inflammatory Response in Staphylococcus aureus Skin and Soft Tissue Infections, Bacteremia, and Subclinical Colonization. 2580 33

Nucleotide-activated effector deployment, prototyped by interferon-dependent immunity, is a common mechanistic theme shared by immune systems of several animals and prokaryotes. Prokaryotic versions include CRISPR-Cas with the CRISPR polymerase domain, their minimal variants, and systems with second messenger oligonucleotide or dinucleotide synthetase (SMODS). Cyclic or linear oligonucleotide signals in these systems help set a threshold for the activation of potentially deleterious downstream effectors in response to invader detection. We establish such a regulatory mechanism to be a more general principle of immune systems, which can also operate independently of such messengers. Using sensitive sequence analysis and comparative genomics, we identify 12 new prokaryotic immune systems, which we unify by this principle of threshold-dependent effector activation. These display regulatory mechanisms paralleling physiological signaling based on 3'-5' cyclic mononucleotides, NAD+-derived messengers, two- and one-component signaling that includes histidine kinase-based signaling, and proteolytic activation. Furthermore, these systems allowed the identification of multiple new sensory signal sensory components, such as a tetratricopeptide repeat (TPR) scaffold predicted to recognize NAD+-derived signals, unreported versions of the STING domain, prokaryotic YEATS domains, and a predicted nucleotide sensor related to receiver domains. We also identify previously unrecognized invader detection components and effector components, such as prokaryotic versions of the Wnt domain. Finally, we show that there have been multiple acquisitions of unidentified STING domains in eukaryotes, while the TPR scaffold was incorporated into the animal immunity/apoptosis signal-regulating kinase (ASK) signalosome.IMPORTANCE Both prokaryotic and eukaryotic immune systems face the dangers of premature activation of effectors and degradation of self-molecules in the absence of an invader. To mitigate this, they have evolved threshold-setting regulatory mechanisms for the triggering of effectors only upon the detection of a sufficiently strong invader signal. This work defines general templates for such regulation in effector-based immune systems. Using this, we identify several previously uncharacterized prokaryotic immune mechanisms that accomplish the regulation of downstream effector deployment by using nucleotide, NAD+-derived, two-component, and one-component signals paralleling physiological homeostasis. This study has also helped identify several previously unknown sensor and effector modules in these systems. Our findings also augment the growing evidence for the emergence of key animal immunity and chromatin regulatory components from prokaryotic progenitors.
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PMID:Identification of Uncharacterized Components of Prokaryotic Immune Systems and Their Diverse Eukaryotic Reformulations. 3295 33