Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “effector”

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 1,135 records · Page 63Linked to original sources
PubMed1992

A site on rod G protein alpha subunit that mediates effector activation.

The heterotrimeric guanine nucleotide binding proteins (G proteins) are activated by sensory or hormone receptors. In turn, the G proteins activate effector proteins such as adenylyl cyclase, cyclic guanosine 3',5'-monophosphate phosphodiesterase (cGMP PDE), phospholipase C, and potassium and calcium ion channels by mechanisms that are poorly understood. A site on the alpha subunit of the G protein transducin (alpha t) has been identified that interacts with and activates cGMP phosphodiesterase, the effector enzyme in rod photoreceptors. A 22-amino acid peptide, corresponding to residues 293 to 314 from the COOH-terminal region of alpha t, fully mimicked alpha t and potently activated PDE. This region is adjacent to the receptor activation domain; thus, the alpha subunit of this G protein has a site for interaction with both its effector and receptor that maps near the COOH-terminus.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1999

Linear differentiation of cytotoxic effectors into memory T lymphocytes.

A central question in immunology is the origin of long-lived T cell memory that confers protection against recurrent infection. The differentiation of naïve T cell receptor transgenic CD8+ cells into effector cytotoxic T lymphocytes (CTLs) and memory CD8+ cells was studied. Memory CD8+ cells that were generated after strong antigenic stimulation were the progeny of cytotoxic effectors and retained antigen-specific cytolytic activity 10 weeks after adoptive transfer to antigen-free recipient mice. Thus, potential vaccines based on CTL memory will require the differentiation of naïve cells into post-effector memory T cells.

Adoptive Transfer↗
PubMed1988

Guanosine triphosphatase activating protein (GAP) interacts with the p21 ras effector binding domain.

A cytoplasmic protein that greatly enhances the guanosine triphosphatase (GTPase) activity of N-ras protein but does not affect the activity of oncogenic ras mutants has been recently described. This protein (GAP) is shown here to be ubiquitous in higher eukaryotes and to interact with H-ras as well as with N-ras proteins. To identify the region of ras p21 with which GAP interacts, 21 H-ras mutant proteins were purified and tested for their ability to undergo stimulation of GTPase activity by GAP. Mutations in nonessential regions of H-ras p21 as well as mutations in its carboxyl-terminal domain (residues 165-185) and purine binding region (residues 117 and 119) did not decrease the ability of the protein to respond to GAP. In addition, an antibody against the carboxyl-terminal domain did not block GAP activity, supporting the conclusion that GAP does not interact with this region. Transforming mutations at positions 12, 59, and 61 (the phosphoryl binding region) abolished GTPase stimulation by GAP. Point mutations in the putative effector region of ras p21 (amino acids 35, 36, and 38) were also insensitive to GAP. However, a point mutation at position 39, shown previously not to impair effector function, did not alter GAP-p21 interaction. These results indicate that GAP interaction may be essential for ras p21 biological activity and that it may be a ras effector protein.

Amino Acid Sequence↗
PubMed2006

OspF and OspC1 are Shigella flexneri type III secretion system effectors that are required for postinvasion aspects of virulence.

Shigella flexneri is the causative agent of dysentery, and its pathogenesis is mediated by a type III secretion system (T3SS). S. flexneri secretes effector proteins into the eukaryotic cell via the T3SS, and these proteins usurp host cellular functions to the benefit of the bacteria. OspF and OspC1 are known to be secreted by S. flexneri, but their functions are unknown. We transformed S. flexneri with a plasmid that expresses a two-hemagglutinin tag (2HA) in frame with OspF or OspC1 and verified that these proteins are secreted in a T3SS-dependent manner. Immunofluorescence of HeLa cells infected with S. flexneri expressing OspF-2HA or OspC1-2HA revealed that both proteins localize in the nucleus and cytoplasm of host cells. To elucidate the function of these T3SS effectors, we constructed DeltaospF and DeltaospC1 deletion mutants by allelic exchange. We found that DeltaospF and DeltaospC1 mutants invade host cells and form plaques in confluent monolayers similar to wild-type S. flexneri. However, in the polymorphonuclear (PMN) cell migration assay, a decrease in neutrophil migration was observed for both mutants in comparison to the migration of wild-type bacteria. Moreover, infection of polarized T84 intestinal cells infected with DeltaospF and DeltaospC1 mutants resulted in decreased phosphorylation of extracellular signal-regulated kinase 1/2 in comparison to that of T84 cells infected with wild-type S. flexneri. To date, these are the first examples of T3SS effectors implicated in mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathway activation. Ultimately, OspF and OspC1 are essential for PMN transepithelial migration, a phenotype associated with increased inflammation and bacterial access to the submucosa, which are fundamental aspects of S. flexneri pathogenesis.

Animals↗
PubMed2006

The translocated Salmonella effector proteins SseF and SseG interact and are required to establish an intracellular replication niche.

The facultative intracellular pathogen Salmonella enterica causes a variety of diseases, including gastroenteritis and typhoid fever. Inside epithelial cells, Salmonella replicates in vacuoles, which localize in the perinuclear area in close proximity to the Golgi apparatus. Among the effector proteins translocated by the Salmonella pathogenicity island 2-encoded type III secretion system, SifA and SseG have been shown necessary but not sufficient to ensure the intracellular positioning of Salmonella vacuoles. Hence, we have investigated the involvement of other secreted effector proteins in this process. Here we show that SseF interacts functionally and physically with SseG but not SifA and is also required for the perinuclear localization of Salmonella vacuoles. The observations show that the intracellular positioning of Salmonella vacuoles is a complex phenomenon resulting from the combined action of several effector proteins.

Animals↗
PubMed1977

Effector cell involved in cell-mediated cytotoxicity to cells infected with herpes simplex virus type 1.

Experiments were performed to analyze the characteristics of the effector cells involved in cell-mediated killing of herpes-infected fibroblasts. Effector cells were fractionated according to adherence and phagocytic properties, and lymphocytes were depleted of T-cells, and EA- and EAC- (antibody-coated bovine erythrocytes and bovine erythrocytes coated with rabbit anti-bovine antibodies and C5-deficient mouse serum, respectively) rosette-forming cells by differential centrifugation. Column passage was used as an alternative to depletion of B-cells and F(c)-receptor-positive cells. Antibody-dependent, cell-mediated cytotoxicity was found to be associated with nonphagocytic cells carrying low-avidity F(c) receptors. Some of these had surface immunoglobulin; others lacked both B- and T-cell markers. Low levels of killing were found without addition of anti-herpes antibody to the test system, and this killing seemed to depend on cells belonging to the same subpopulation as the antibody-dependent effector cells.

B-Lymphocytes↗
PubMed1977

Cell-mediated immunity to tumor antigen in Marek's disease: susceptibility of effector cells to antithymocyte serum and enhancement of cytotoxic activity by Vibrio cholerae neuraminidase.

Spleen cells from chickens inoculated 7 to 8 days previously with Marek's disease virus were cytotoxic for 51Cr-labeled cells of a Marek's disease lymphoblastoid cell line (MSB-1 line) in a 4-h in vitro cytotoxic assay. The cytotoxic activity of spleen cells was inhibited by pretreatment with antithymocyte serum and complement, but not with complement alone or in combination with anti-bursa cell serum or normal preimmune serum. The conclusion was that the effector cell in the above cytotoxic assay was a thymus-derived lymphocyte. Also, pretreatment of target cells with Vibrio cholerae neuraminidase enhanced in vitro cytotoxic activity of effector cells. Similar enzymatic treatment of effector cells had a negligible effect on cytotoxicity.

Animals↗
PubMed1981

Natural killer cell activity in chickens: target cell analysis and effect of antithymocyte serum on effector cells.

A battery of lymphoid and nonlymphoid cells was examined for susceptibility to lysis by natural killer cells of chickens. Several susceptible targets were recognized, and most susceptible among these were cells of line LSCC-RP9, derived from a lymphoid tumor induced by Rous-associated virus 2. The natural killer reactivity against LSCC-RP9 target cells did not appear to be directed against an antigen(s) induced by Rous-associated virus 2 because other lymphoid and nonlymphoid cells infected with this were resistant to lysis in vitro by natural killer cells. The effector cells of natural killer reactivity in chickens were refractory to treatment with potent anti-T-cell and anti-B-cell sera. Inoculation of Marek's disease virus in line 15 X 7 chickens resulted in enhanced natural killer cell activity, and the effector cells of this enhanced activity, and the effector cells of this enhanced activity were also resistant to anti-T-cell serum.

Animals↗
PubMed1983

Natural cell-mediated cytotoxicity against Candida albicans induced by cyclophosphamide: nature of the in vitro cytotoxic effector.

We have recently reported the in vivo modulation of resistance to experimental Candida albicans infection by cyclophosphamide (150 mg/kg intraperitoneally) in mice and have shown that increased resistance to the microbial challenge occurs 12 to 21 days after treatment with the drug (Bistoni et al., Infect. Immun. 40: 46-55, 1983). The event is accompanied by the appearance of a highly candidacidal cell population in the spleen and the activation of a subpopulation of natural cytotoxic effectors reactive in vitro against YAC-1 tumor cells. We now provide evidence that these anti-YAC-1 cytotoxic effectors are clearly distinct from the cyclophosphamide-induced candidacidal effectors, which seem to belong to a macrophage-monocyte lineage. The enhanced cytotoxic activity induced by cyclophosphamide was not restricted to C. albicans but was also exerted against a panel of Candida strains.

Animals↗
PubMed1991

Potentiation of human natural killer cell cytotoxicity by Salmonella bacteria is an interferon- and interleukin-2-independent process that utilizes CD2 and CD18 structures in the effector phase.

Incubation of large granular lymphocytes (LGL) with glutaraldehyde-fixed bacteria stimulated in the supernatant the production of interferon (IFN), which proved to be mainly IFN-gamma. Even though IFN-gamma was produced upon exposure of LGL to bacteria, anti-IFN-gamma antibodies failed to interfere with induction of cytotoxicity by bacterial contact. Anti-IFN-gamma receptor antibodies had no effect on the induction of activated killing by bacterial contact either. We also tested the effect of anti-IFN-alpha antibody, but it failed to interfere with induction of cytotoxicity by bacterial contact. No interleukin-2 (IL-2) was detected in the culture supernatant of bacterially activated LGL by the mouse HT2 cell assay, nor did we detect any IL-2 mRNA in bacterially activated LGL by Northern RNA blot assay. Neutralizing anti-IL-2 antiserum had no effect on the induction of activated killing by bacterial contact, and recombinant IL-4 did not interfere with the induction of activated killing. We then studied the membrane structures involved in bacterially activated killing. Anti-CD18 monoclonal antibody did not interfere with the induction phase of bacterially activated killing. However, both anti-CD18 and anti-CD2 antibodies inhibited the effector phase of bacterially activated killing. The effector pathways utilized by activated LGL depended on the mode of activation in that even though bacterially activated LGL were sometimes blocked by anti-CD2 monoclonal antibody, recombinant-IL-2-stimulated LGL were not. In conclusion, our present results suggest that there may be mediators other than exogenously secreted IFNs and IL-2 which are responsible for the induction of activated killing after bacterial contact. CD18 and CD2 structures were shown to be involved in the effector phase of bacterially activated killing.

Antibodies, Monoclonal↗
PubMed1999

Yersinia pseudotuberculosis-induced calcium signaling in neutrophils is blocked by the virulence effector YopH.

Pathogenic species of the genus Yersinia evade the bactericidal functions of phagocytes. This evasion is mediated through their virulence effectors, Yops, which act within target cells. In this study we investigated the effect of Yersinia pseudotuberculosis on Ca2+ signaling in polymorphonuclear neutrophils. The intracellular free calcium concentration in single adherent human neutrophils was monitored during bacterial infection and, in parallel, the encounter between the bacteria and cells was observed. When a plasmid-cured strain was used for infection, adherence of a single bacterium to the cellular surface induced a beta1 integrin-dependent transient increase in the intracellular concentration of free calcium. This was, however, not seen with Yop-expressing wild-type bacteria, which adhered to the cell surface without generating any Ca2+ signal. Importantly, the overall Ca2+ homeostasis was not affected by the wild-type strain; the Ca2+ signal mediated by the G-protein-coupled formyl-methionyl-leucyl-phenylalanine receptor was still functioning. Hence, the blocking effect was restricted to certain receptors and their signaling pathways. The use of different Yop mutant strains revealed that the protein tyrosine phosphatase YopH was responsible for the inhibition. This virulence determinant has previously been implicated in very rapid Yersinia-mediated effects on target cells as the key effector in the blockage of phagocytic uptake. The present finding, that Y. pseudotuberculosis, via YopH, specifically inhibits a self-induced immediate-early Ca2+ signal in neutrophils, offers more-detailed information concerning the effectiveness of this virulence effector and implies an effect on Ca2+-dependent, downstream signals.

Bacterial Adhesion↗
PubMed2000

Salmonella enterica serovar typhimurium-dependent regulation of inducible nitric oxide synthase expression in macrophages by invasins SipB, SipC, and SipD and effector SopE2.

When Salmonella enterica invades mammalian cells, it activates signals leading to increased expression of inflammatory mediators. One such mediator is nitric oxide (NO), which is produced under control of the enzyme inducible NO synthase (iNOS). Induction of iNOS in response to Salmonella infection has been demonstrated, but the bacterial effector molecules that regulate expression of the enzyme have not been identified. In the study reported here, an analysis of Salmonella-dependent iNOS expression in macrophages was carried out. Wild-type Salmonella strains increased the levels of both iNOS protein and mRNA in murine macrophage cell lines in an invasion-independent fashion. Mutant strains lacking a functional pathogenicity island 1-encoded type III secretion system, as well as strains lacking the invasins SipB, SipC, and SipD, were impaired in iNOS induction. Complementation experiments indicated that all three of the invasins were required for induction of iNOS expression. These results suggested that an effector protein, translocated into macrophages via the type III secretion system in a SipB-, SipC-, and SipD-dependent manner, might be the ultimate mediator of iNOS induction. In keeping with this idea, a mutant strain deficient in SopE2, a recently described homolog of SopE, was found to be impaired in the induction of iNOS expression. These observations suggest that iNOS expression is regulated by signals activated by SopE2 (and possibly SopE) and that the role of SipB, SipC, and SipD in this process is to facilitate translocation of the relevant effector.

Animals↗
PubMed2001

Immune response induction and new effector mechanisms possibly involved in protection conferred by the Cuban anti-meningococcal BC vaccine.

This report explores the participation of some afferent mechanisms in the immune response induced by the Cuban anti-meningococcal vaccine VA-MENGOC-BC. The induction of delayed-type hypersensitivity in nursing babies and lymphocyte proliferation after immunization is demonstrated. The presence of gamma interferon IFN-gamma and interleukin-2 (IL-2) mRNAs but absence of IL-4, IL-5, and IL-10 mRNAs were observed in peripheral blood mononuclear cells from immunized subjects after in vitro challenge with outer membrane vesicles. In addition, some effector functions were also explored. The presence of opsonic activity was demonstrated in sera from vaccinees. The role of neutrophils as essential effector cells was shown. In conclusion, we have shown that, at least in the Cuban adult population, VA-MENGOC-BC induces mechanisms with a T-helper 1 pattern in the afferent and effector branches of the immune response.

Adult↗
PubMed2003

The Salmonella enterica serovar typhimurium translocated effectors SseJ and SifB are targeted to the Salmonella-containing vacuole.

The Salmonella enterica serovar Typhimurium type III secretion system (TTSS) encoded in Salmonella pathogenicity island 2 (SPI-2) promotes replication within host cells and systemic infection of mice. The SPI-2 TTSS is expressed following Salmonella internalization into host cells and translocates effectors across the membrane of the Salmonella-containing vacuole (SCV). Two effectors with similar amino-terminal domains, SseJ and SifB, localize to the SCV membrane in infected HEp-2 cells and subsequently traffic away from the SCV along Salmonella-induced-filaments (Sifs). Following infection of RAW cells, SseJ and SifB localize to the SCV as well as LAMP-1-positive, vesicular-appearing structures distant from the SCV. Trafficking of SseJ and SifB away from the SCV requires the SPI-2 effector SifA. Deletion of sseJ, but not sifB, leads to attenuation of Salmonella replication in mice following intraperitoneal inoculation. The contribution of SseJ to in vivo replication is identical in wild-type and sifA deletion backgrounds, suggesting that SseJ trafficking away from the SCV along Sifs is unnecessary for its virulence function.

Animals↗
PubMed2004

Role of the Salmonella pathogenicity island 1 effector proteins SipA, SopB, SopE, and SopE2 in Salmonella enterica subspecies 1 serovar Typhimurium colitis in streptomycin-pretreated mice.

Salmonella enterica subspecies 1 serovar Typhimurium (serovar Typhimurium) induces enterocolitis in humans and cattle. The mechanisms of enteric salmonellosis have been studied most extensively in calf infection models. The previous studies established that effector protein translocation into host cells via the Salmonella pathogenicity island 1 (SPI-1) type III secretion system (TTSS) is of central importance in serovar Typhimurium enterocolitis. We recently found that orally streptomycin-pretreated mice provide an alternative model for serovar Typhimurium colitis. In this model the SPI-1 TTSS also plays a key role in the elicitation of intestinal inflammation. However, whether intestinal inflammation in calves and intestinal inflammation in streptomycin-pretreated mice are induced by the same SPI-1 effector proteins is still unclear. Therefore, we analyzed the role of the SPI-1 effector proteins SopB/SigD, SopE, SopE2, and SipA/SspA in elicitation of intestinal inflammation in the murine model. We found that sipA, sopE, and, to a lesser degree, sopE2 contribute to murine colitis, but we could not assign an inflammation phenotype to sopB. These findings are in line with previous studies performed with orally infected calves. Extending these observations, we demonstrated that in addition to SipA, SopE and SopE2 can induce intestinal inflammation independent of each other and in the absence of SopB. In conclusion, our data corroborate the finding that streptomycin-pretreated mice provide a useful model for studying the molecular mechanisms of serovar Typhimurium colitis and are an important starting point for analysis of the molecular events triggered by SopE, SopE2, and SipA in vivo.

Animals↗
PubMed2005

In vitro effector activity of Pneumocystis murina-specific T-cytotoxic-1 CD8+ T cells: role of granulocyte-macrophage colony-stimulating factor.

Human immunodeficiency virus (HIV)-related opportunistic infections continue to occur in patients who are newly diagnosed with HIV infection, those in the early course of highly active antiretroviral therapy or nonadherent to HIV care, and other immunosuppressed individuals. One of the most common opportunistic infections in these patients is Pneumocystis pneumonia. CD8+ T cells are recruited to the lung after P. carinii infection and have been associated with both lung injury and host defense. This variability may be due to subpopulations of CD8+ T cells recruited to the lung. We have previously shown using adoptive transfer studies that in vivo-generated T-cytotoxic-1 (Tc1) CD8+ T cells, defined by the secretion of gamma interferon (IFN-gamma), have effector activity against Pneumocystis spp. in vitro as well as in vivo. To better understand the mechanisms of these effects, we generated, expanded, and tested Tc1 and Tc2 CD8+ T cells specific for P. murina ex vivo. Tc1-polarized CD8+ T cells secreted higher levels of IFN-gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF) and lower levels of interleukin-4 (IL-4), IL-5, IL-10, and IL-13 than Tc2 CD8+ T cells when stimulated with P. murina antigen. Moreover, Tc1 CD8+ T cells demonstrated enhanced effector activity in a macrophage-mediated killing assay which was independent of cell contact. The augmentation in macrophage-mediated P. murina killing was significantly abrogated when GM-CSF was neutralized in the Tc1 CD8+ T cells. These data support the possibility that antigen-specific GM-CSF secretion is critical for effector activity of P. murina-specific Tc1 CD8+ T cells in vitro.

Animals↗
PubMed2006

Pseudomonas syringae HrpJ is a type III secreted protein that is required for plant pathogenesis, injection of effectors, and secretion of the HrpZ1 Harpin.

The bacterial plant pathogen Pseudomonas syringae requires a type III protein secretion system (TTSS) to cause disease. The P. syringae TTSS is encoded by the hrp-hrc gene cluster. One of the genes within this cluster, hrpJ, encodes a protein with weak similarity to YopN, a type III secreted protein from the animal pathogenic Yersinia species. Here, we show that HrpJ is secreted in culture and translocated into plant cells by the P. syringae pv. tomato DC3000 TTSS. A DC3000 hrpJ mutant, UNL140, was greatly reduced in its ability to cause disease symptoms and multiply in Arabidopsis thaliana. UNL140 exhibited a reduced ability to elicit a hypersensitive response (HR) in nonhost tobacco plants. UNL140 was unable to elicit an AvrRpt2- or AvrB1-dependent HR in A. thaliana but maintained its ability to secrete AvrB1 in culture via the TTSS. Additionally, UNL140 was defective in its ability to translocate the effectors AvrPto1, HopB1, and AvrPtoB. Type III secretion assays showed that UNL140 secreted HrpA1 and AvrPto1 but was unable to secrete HrpZ1, a protein that is normally secreted in culture in relatively large amounts, into culture supernatants. Taken together, our data indicate that HrpJ is a type III secreted protein that is important for pathogenicity and the translocation of effectors into plant cells. Based on the failure of UNL140 to secrete HrpZ1, HrpJ may play a role in controlling type III secretion, and in its absence, specific accessory proteins, like HrpZ1, may not be extracellularly localized, resulting in disabled translocation of effectors into plant cells.

Arabidopsis↗
PubMed1992

KdpD and KdpE, proteins that control expression of the kdpABC operon, are members of the two-component sensor-effector class of regulators.

The Kdp system of Escherichia coli, a transport ATPase with high affinity for potassium, is expressed when turgor pressure is low. Expression requires KdpD, a 99-kDa membrane protein, and KdpE, a 25-kDa soluble cytoplasmic protein. The sequences of KdpD and KdpE show they are members of the sensor-effector class of regulatory proteins: the C-terminal half of KdpD is homologous to sensors such as EnvZ and PhoR, and KdpE is homologous to effectors such as OmpR and PhoB. The predicted structure of KdpD suggests that it is anchored to the membrane by four membrane-spanning segments near its middle, with both C- and N-terminal portions in the cytoplasm. Subcellular fractionation confirms the expected location of the protein in the inner membrane. The N-terminal region has no homology to known proteins and is the site of mutations that make Kdp expression partially constitutive; this portion may serve to sense turgor pressure. Since several other sensor-effectors have been shown to mediate control through phosphorylation, this mechanism is proposed to control expression of Kdp.

Adenosine Triphosphatases↗