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PubMed2006

Tissue-tropic effector T cells: generation and targeting opportunities.

The localization of effector T cells to extralymphoid tissues is crucial for the generation of an effective immune response, but it also underlies many autoimmune and inflammatory disorders. Recent studies have highlighted a central role for draining lymph nodes and environmentally imprinted dendritic cells in the generation of tissue-tropic effector T cells. Here, I outline our current understanding of the mechanisms that regulate the generation and localization of tissue-tropic effector T cells, and the potential ways in which these pathways can be exploited for immunotherapeutic purposes.

Animals↗
PubMed2006

The effector caspases drICE and dcp-1 have partially overlapping functions in the apoptotic pathway in Drosophila.

Caspases are essential components of the apoptotic machinery in both vertebrates and invertebrates. Here, we report the isolation of a mutant allele of the Drosophila effector caspase drICE as a strong suppressor of hid- (head involution defective-) induced apoptosis. This mutant was used to determine the apoptotic role of drICE. Our data are consistent with an important function of drICE for developmental and irradiation-induced cell death. Epistatic analysis suggests that drICE acts genetically downstream of Drosophila inhibitor of apoptosis protein 1 (Diap1). However, although cell death is significantly reduced in drICE mutants in all assays, it is not completely blocked. A double-mutant analysis between drICE and death caspase-1 (dcp-1), another effector caspase, reveals that some cells (type I) strictly require drICE for apoptosis, whereas other cells (type II) require either drICE or dcp-1. Thus, these data demonstrate a barely appreciated complexity in the apoptotic pathway, and are consistent with current models about effector caspase regulation in both vertebrates and invertebrates.

Amino Acid Sequence↗
PubMed2006

Systems analysis of effector caspase activation and its control by X-linked inhibitor of apoptosis protein.

Activation of effector caspases is a final step during apoptosis. Single-cell imaging studies have demonstrated that this process may occur as a rapid, all-or-none response, triggering a complete substrate cleavage within 15 min. Based on biochemical data from HeLa cells, we have developed a computational model of apoptosome-dependent caspase activation that was sufficient to remodel the rapid kinetics of effector caspase activation observed in vivo. Sensitivity analyses predicted a critical role for caspase-3-dependent feedback signalling and the X-linked-inhibitor-of-apoptosis-protein (XIAP), but a less prominent role for the XIAP antagonist Smac. Single-cell experiments employing a caspase fluorescence resonance energy transfer substrate verified these model predictions qualitatively and quantitatively. XIAP was predicted to control this all-or-none response, with concentrations as high as 0.15 microM enabling, but concentrations >0.30 microM significantly blocking substrate cleavage. Overexpression of XIAP within these threshold concentrations produced cells showing slow effector caspase activation and submaximal substrate cleavage. Our study supports the hypothesis that high levels of XIAP control caspase activation and substrate cleavage, and may promote apoptosis resistance and sublethal caspase activation in vivo.

Apoptosis↗
PubMed1998

Effector domain mutants of Rho dissociate cytoskeletal changes from nuclear signaling and cellular transformation.

The small GTP-binding Rho proteins control a variety of biological activities, including organization of the actin cytoskeleton, regulation of gene expression and cellular transformation. In contrast, Ras proteins do not induce actin stress fibers, but potently transform cells which exhibit a morphology clearly distinct from that caused by activated forms of Rho. To investigate whether nuclear signaling and oncogenic potential of Rho are a consequence of its profound effect on cytoskeletal organization, we replaced each amino acid in the Rho effector loop with those of Ras, or replaced conserved residues with others known to result in differential signaling capability when introduced into Ras and Rac1. These Rho mutants did not gain the ability to induce the MAPK, JNK or p38 pathways but, surprisingly, all Rho effector loop mutants still continued to induce actin stress fiber formation. However, three of these Rho mutants, with substitutions of leucine-39, glutamic acid-39, or cysteine-42, lost the ability to stimulate gene transcription via the serum response factor (SRF) and failed to induce neoplastic transformation. Thus, these results indicate that cytoskeletal changes are not sufficient to induce the transformed phenotype, and that Rho-effector molecules regulating the actin cytostructure are distinct from those signaling to the nucleus and subverting normal growth control.

3T3 Cells↗
PubMed1998

Regulation of myeloid cell growth by distinct effectors of Ras.

To examine the biochemical pathways by which activated Ha-Ras(G12V) (Ha-RasV12) induces factor-independent growth of myeloid cells, Ha-Ras effector loop mutations, including Y40C, T35S, and E37G, were analysed in a mouse factor-dependent myeloid cell line, WT19. Expression of a single effector loop mutant, Ha-Ras(G12V, Y40C) (Ha-RasV12C40), inhibited factor-withdrawal apoptosis, suggesting that activation of the phosphatidylinositol 3'-kinase (Pl3K) pathway is essential to prevent cell death. Neither Ha-Ras (G12V, T35S) (Ha-RasV12S35), which activates the Rafl signaling pathway, nor Ha-Ras(G12V, E37G) (Ha-RasV12G37), which stimulates the RalGDS pathway, did not have significant effects on factor-withdrawal apoptosis of myeloid cells. Although Ha-RasV12C40 inhibited apoptosis, it did not stimulate entry into the cell cycle. Cell lines containing the combination of Ha-RasV12G37 and Ha-RasV12C40 were capable of factor-independent cell growth, while expression of the other combinations of the Ha-Ras effector mutants were not. The combined expression of Bcl-2 and Ha-RasV12G37 was not sufficient to stimulate factor independent growth, suggesting that Ha-RasV12C40 activates additional signals, besides blocking apoptosis, which are critical for factor-independent growth of myeloid cells. In factor-starved myeloid cells, inducible expression of Ha-RasV12G37 results in decreased level of p27Kip1 protein, a cyclin-dependent kinase inhibitor (CKI). These data suggest that the factor-independent growth of myeloid cells requires the activation of at least two pathways, one inhibiting factor-withdrawal apoptosis, and another causing cell cycle progression.

Amino Acid Substitution↗
PubMed2002

Induction of human MDR1 gene expression by 2-acetylaminofluorene is mediated by effectors of the phosphoinositide 3-kinase pathway that activate NF-kappaB signaling.

The expression of P-glycoprotein encoded by the multidrug resistance (MDR1) gene is associated with the emergence of the MDR phenotype in cancer cells. Human MDR1 and its rodent homolog mdr1a and mdr1b are frequently overexpressed in liver cancers. However, the underlying mechanisms are largely unknown. The hepatocarcinogen 2-acetylaminofluorene (2-AAF) efficiently activates rat mdr1b expression in cultured cells and in Fisher 344 rats. We recently reported that activation of rat mdr1b in cultured cells by 2-AAF involves a cis-activating element containing a NF-kappaB binding site located -167 to -158 of the rat mdr1b promoter. 2-AAF activates IkappaB kinase (IKK), resulting in degradation of IkappaBbeta and activation of NF-kappaB. In this study, we report that 2-AAF could also activate the human MDR1 gene in human hepatoma and embryonic fibroblast 293 cells. Induction of MDR1 by AAF was mediated by DNA sequence located at -6092 which contains a NF-kappaB binding site. Treating hepatoma cells with 2-AAF activated phosphoinositide 3-kinase (PI3K) and its downstream effectors Rac1, and NAD(P)H oxidase. Transient transfection assays demonstrated that constitutively activated PI3K and Rac1 enhanced the activation of the MDR1 promoter by 2-AAF. Treatment of hepatoma cells with 2-AAF also activated another PI3K downstream effector Akt. Transfection of recombinant encoding a dominant activated Akt also enhanced the activation of MDR1 promoter activation by 2-AAF. These results demonstrated that 2-AAF up-regulates MDR1 expression is mediated by the multiple effectors of the PI3K signaling pathway.

2-Acetylaminofluorene↗
PubMed1986

The lipoprotein lipase of white adipose tissue. Changes in the adipocyte cell-surface content of enzyme in response to extracellular effectors in vitro.

An indirect labelled-second-antibody cellular immunoassay for adipocyte surface lipoprotein lipase was used to assess the changes that occurred during the incubation of cells in the presence and absence of effectors. In the absence of any specific effectors, the amount of immunodetectable lipoprotein lipase present at the surface of adipocytes remained constant throughout the 4 h incubation period at 37 degrees C. Under such conditions total cellular enzyme activity also remained constant, with no activity appearing in the medium. In the presence of heparin, cell-surface immunodetectable lipoprotein lipase increased by up to 20%, whereas in the presence of cycloheximide they decreased by up to 60%. Thus the obvious turnover of enzyme from this cell-surface site was found to be relatively rapid and dependent for its replenishment, at least in part, on protein synthesis. In the presence of insulin alone, a substantial increase in cell-surface lipoprotein lipase protein occurred, only part of which was dependent on protein synthesis. The total cellular activity of lipoprotein lipase was unaffected by the presence of insulin. The insulin-dependent increase in cell-surface enzyme was potentiated somewhat in the presence of dexamethasone, which was not shown to exert any independent effect. Glucagon, adrenaline and theophylline all produced a significant decline in the cell-surface immunodetectable lipoprotein lipase, which in the case examined (adrenaline) was partially additive with regard to the independent effect of cycloheximide. Cell-surface immunodetectable lipoprotein lipase amounts were decreased significantly when cells were incubated in the presence of either colchicine or tunicamycin. The concerted way in which cell-surface lipoprotein lipase altered during the incubations of adipocytes in the presence of effectors suggested that the translocation of enzyme to and from this cellular site was dependent on hormonal action and the integrity of intracellular protein-transport mechanisms.

Adipose Tissue↗
PubMed1998

Cytotoxic effectors activated by low-dose IL-2 plus IL-12 lyse IL-2-resistant autologous acute myeloid leukaemia blasts.

We have investigated the susceptibility of primary acute myeloid leukaemia (AML) samples to the lytic action of normal peripheral blood mononuclear cells (PBMC), as well as of the patients' autologous and allogeneic PBMC collected at the time of remission following stimulation with different concentrations of interleukin (IL)-2 and IL-12, both alone and in variable combinations. Primary AML blasts were resistant to IL-2-activated PBMC effectors generated from normal individuals, allogeneic and autologous patients in five, six and eight of the 10 AML samples tested, respectively, IL-12 alone proved ineffective in generating anti-leukaemic activity, whereas, in combination, the two cytokines induced anti-leukaemic killing in all five cases resistant to normal PBMC, in 4/6 samples resistant to allogeneic AML effectors and in 5/8 cases resistant to autologous effectors. In each case the lytic effect was maintained at the lowest cytokine combination (10 + 10 IU/ml) utilized. The suggestion of a synergistic effect was further strengthened by the evidence that at the lowest doses of IL-2 and IL-12 the degree of killing was greater than that promoted by each cytokine independently. The results of this study suggest that two major limitations associated with the administration of IL-2 to AML patients, the resistance of the blasts to IL-2-generated killing and the toxicity associated with high-dose IL-2, may be overcome by the combined use of very low doses of IL-2 and IL-12. As IL-2-resistant blasts may be lysed by a low-dose combination of IL-2/IL-12, feasibility studies with this cytokine combination are worthy of exploration in vivo.

Adult↗
PubMed2003

Definition of the HLA-A2 restricted peptides recognized by human CD8+ effector T cells by flow-assisted sorting of the CD8+ CD45RA+ CD28- T cell subpopulation.

In response to antigenic stimulation, naive MHC-class I restricted and antigen-specific CD8+ CD45RA+ CD28+ T cells undergo clonal expansion, differentiate into CD8+ CD45RO+ memory T cells and convert to CD8+ CD45RA+ CD28- T cells displaying potent immune effector functions upon re-encounter with the nominal antigen. We show that the effector CD8+ CD45RA+ CD28- T cell subset is expanded in peripheral blood lymphocytes (PBL) from patients with human papilloma virus (HPV)+ cervical lesions as well as in PBL from patients with pulmonary tuberculosis. Flow-cytometric cell sorted CD8+ CD45RA+ CD28- and CD8+ CD45RA+ CD28- T cells were tested for recognition of HLA-A2 restricted peptides derived either from the human papillomavirus (HPV)16-E7 gene product, or from M. tuberculosis antigens. Mostly CD8+ CD45+ CD28- T cells define antigen/peptide-specific and MHC-restricted responses. These data were confirmed in PBL from patients with tuberculosis using HLA-A2 tetramer-complexes loaded with a peptide from the M. tuberculosis Ag85b antigen by flow cytometry. The sorting of this T cell subset enables to determine the fine specificity of CD8+ effector T cells without the need for in vitro manipulation.

Antigen-Antibody Reactions↗
PubMed2003

The Bcl-2 family pro-apoptotic molecule, BNIP3 regulates activation-induced cell death of effector cytotoxic T lymphocytes.

BNIP3 is a recently described pro-apoptotic member of the Bcl-2 family and in BNIP3 cDNA-transfected cell lines, cell death occurs via a caspase-independent pathway with opening of the mitochondrial permeability transition (PT) pore and rapid loss of mitochondrial transmembrane potential (Delta psi m). However, its expression or function in physiologic cell types is not known. Our results using the T-cell receptor transgenic mice P14, specific for lymphocyte choreomeningitis virus (LCMV) glycoprotein, show that in contrast to the other Bcl-2 family pro-apoptotic molecules, BNIP3 is transcriptionally highly up-regulated in effector cytotoxic T lymphocytes (CTL). Because CTL have a propensity to undergo activation-induced cell death (AICD) upon restimulation, we tested for other features associated with BNIP3-induced cell death. AICD of CTL was caspase-independent as determined by measuring caspase activation during target cell killing as well as by lack of inhibition with caspase inhibitors. Moreover, similar to BNIP3-induced cell death, CTL apoptosis was associated with increased production of reactive oxygen species and decreased Delta psi m. Finally, retroviral transduction of BNIP3 antisense RNA diminished AICD in effector CTL. These results suggest that BNIP3 may play an important role in T-cell homeostasis by regulating effector CTL numbers.

Amino Acid Chloromethyl Ketones↗
PubMed1997

Some thoughts on the response to antigens that are effector T-helper independent ('thymus independence')

The Self-Non-Self discrimination is germline-selected for defence mechanisms ('innate immune systems') whereas it is somatically learned for immune systems ('adaptive immune systems'). It is proposed that immune system evolved from defence mechanisms by adding large recognitive repertoires that, by aggregating with antigens, were able to trigger the already existent effector functions of defence mechanisms. Thus today there are two pathways to triggering each class of effector function (macrophage opsonization, complement lysis or natural killer/-natural cytotoxic cell activity). The antigen-antibody complex and the T-cell antigen-receptor interaction trigger the immune pathway: the receptors of the defence mechanism trigger the 'alternate' or 'innate' pathway. The evolutionary selection pressure on defence mechanisms was to increase the size of the recognitive repertoire, which in turn, necessitated the emergence of a somatically learned Self-Non-Self discrimination. By contrast with defence mechanisms that are triggered effector T-helper (eTh) independently by polymers (Signal[3]), immune systems can be activated by monomers, a pathway that requires associative recognition of monomer and the reading of two Signals, Signal[1] resulting from the binding of an epitope to the antigen-receptor complex, Signal[2] delivered by an eTh cell. The evolving immune system hijacked part of this eTh-independent pathway (Signal[3]) into which Signal ([1] + [2]) merged. A model of these relationships is proposed.

Animals↗
PubMed2001

Effector cytolotic function but not IFN-gamma production in cytotoxic T cells triggered by virus-infected target cells in vitro.

Cytolysis and interferon(IFN)-gamma production are two independent effector functions of activated cytotoxic T (Tc) cells. We have used the Tc-cell response against the flavivirus, Murray Valley encephalitis virus (MVE), to investigate the requirements for inducing these two functions with regard to antigen-concentration and CD8 coreceptor involvement. Cognate peptide-pulsed target cells triggered cytolysis by primary ex vivo MVE-immune as well as in vitro peptide-restimulated splenocytes at lower peptide concentrations than IFNgamma-production (100-fold lower in the case of primary ex vivo effectors). Little difference was observed in CD8 dependency. Importantly, neither of the effector populations were triggered to produce IFN-gamma by virus-infected target cells, although cytolysis occurred. This result raises the possibility that the levels of presentation of cognate antigen on virus-infected cells in vivo may be below the threshold required for the IFN-gamma production.

Animals↗
PubMed1998

Identification of a specific effector of the small GTP-binding protein Rap2.

Rap2 is a small GTP-binding protein that belongs to the Ras superfamily and whose function is still unknown. To elucidate Rap2 function, we searched for potential effectors by screening a mouse brain cDNA library in a yeast two-hybrid system using as a bait a Rap2A protein bearing a mutation of Gly to Val at position 12. This strategy lead to the identification of a protein that interacts specifically with Rap2A complexed with GTP, and requires an intact effector domain of Rap2A for interaction; we designated this protein Rap2-interacting protein 8 (RPIP8). Biochemical data obtained from in vitro studies with purified proteins confirmed the genetic results. Mouse RPIP8 consists of 446 amino acids, bears a coiled-coil domain between residues 265 and 313, and is expressed principally in brain. Its human counterpart, of 400 amino acids, exhibits 93.7% identity in their common region. A search for similar sequences in expressed-sequence-tags databanks revealed the presence in human and rodents of mRNAs encoding the 400-residue and 446-residue forms of RPIP8. Furthermore a doublet of 45-50 kDa, corresponding to the 400-residue and 446-residue forms of the protein, was detected by western blotting of mouse brain extracts and lysates from pheochromocytoma PC12 cells and the pancreatic beta-cell lines HIT-T15 and RIN-m5F. Using transient transfections of HIT-T15 cells it was possible to demonstrate that [Val12]Rap2 and wild-type Rap2 could be immunoprecipitated with RPIP8. These data therefore argue for RPIP8 being a specific effector of the Rap2 protein in cells exhibiting neuronal properties.

Amino Acid Sequence↗
PubMed1999

Influence of cholesterol crystallization effector proteins on vesicle fusion in supersaturated model bile.

BACKGROUND: In lithogenic bile, cholesterol-rich vesicles rapidly aggregate and fuse to eventually form cholesterol crystals. This process is modulated by cholesterol crystallization effector substances. In this study, we developed a method for quantitative assessment of vesicle fusion and used it to partly characterize the mechanisms of action of cholesterol crystallization effector proteins. METHODS: Cholesterol:phospholipid (1:1) liposomes were prepared and labelled with octadecyl rhodamine B chloride (R18). Fusion of these liposomes was detected by the increase of R18 fluorescence after incubation with various proteins, such as albumin, concanavalin-A bound glycoprotein, immunoglobulins, apolipoprotein A-I and apolipoprotein B (all at 100 microg/mL). RESULTS: Fusion of cholesterol/phospholipid liposomes was increased by 16 and 14% in the presence of concanavalin-A bound glycoprotein and immunoglobulins, respectively, and decreased by 21 and 9% after addition of apolipoprotein A-I and apolipoprotein B, respectively. The effect of each protein on vesicle fusion was correlated with its hydrophobicity. CONCLUSIONS: These results suggest that nucleation effector proteins modulate the stability of vesicles and, thus, affect cholesterol crystallization. Such modulation is based upon protein-vesicle association, which defines the physico-chemical metastability of vesicular cholesterol.

Apolipoprotein A-I↗
PubMed2000

Peptide immunization indicates that CD8+ T cells are the dominant effector cells in trinitrophenyl-specific contact hypersensitivity.

The identity of the effector T cell population involved in contact hypersensitivity is still questionable with evidence promoting both CD4+ or CD8+ T cells. Previous experimental studies have relied on the in vivo depletion of T cell subsets using antibody, or the use of knock-out mice with deficiencies in either CD4+ or CD8+ T cell-mediated immunity. To address the role of the class I- and class II-mediated pathways of T cell activation in contact hypersensitivity responses in mice with an intact immune system, we utilized various trinitrophenyl-derivatized peptides, which bind specifically with H-2Kb (major histocompatibility complex class I) or H-2I-Ab (major histocompatibility complex class II). The subcutaneous injection of major histocompatibility complex class II-specific, but not of class I-binding, hapten-derivatized peptides in incomplete Freund's adjuvant induced specific, albeit low, contact hypersensitivity responsiveness to trinitrochlorobenzene. When bone-marrow-derived dendritic cells, however, were pulsed with the same peptides and administered intradermally, the opposite result was observed, namely that the class I binding peptides induced contact hypersensitivity responses similar to that observed after epicutaneous trinitrochlorobenzene application. In contrast, dendritic cells pulsed with major histocompatibility complex class II binding peptides did not reproducibly sensitize for contact hypersensitivity responses. Surprisingly, both immunization protocols efficiently induced CD8+ effector T cells. These results support the notion that CD8+ T cells are the dominant effector population mediating contact hypersensitivity responsiveness and that the CD4+ T cell subset only contributes little if at all.

Animals↗
PubMed2000

Different types of FCgamma-receptors are involved in anti-Lewis Y antibody induced effector functions in vitro.

Stimulation of monocytes by interaction of monoclonal antibodies (mAbs) with Fc gamma receptors (FcgammaRs) results in the activation of various monocyte effector functions. In the present investigation we show that the anti-Lewis Y (LeY) anti-tumour mAb ABL 364 and its mouse/human IgG1 chimaera induce both antibody-dependent cellular cytotoxicity (ADCC) and the release of tumour necrosis factor alpha (TNF-alpha) during mixed culture of monocytes with LeY+ SKBR5 breast cancer cells in vitro. Although anti-LeY mAb-mediated TNF-alpha release paralleled ADCC activity, cytokine release required a higher concentration of sensitizing mAb than the induction of cytolysis. The determination of the FcgammaR classes involved in the induction of the distinct effector functions showed that anti-LeY mAb-induced cytolysis was triggered by interaction between anti-LeY mAbs and FcgammaRI. In contrast, mAb-induced TNF-alpha release mainly depended on the activation of monocyte FcgammaRII. Neutralization of TNF-alpha showed no influence on monocyte ADCC activity towards SKBR5 target cells. Our data indicate an independent regulation of anti-LeY mAb induced effector functions of ADCC and TNF-alpha release which seemed to be triggered by activation of different types of FcgammaR.

Animals↗
PubMed2000

A regulator of G protein signaling interaction surface linked to effector specificity.

Proteins of the regulator of G protein signaling (RGS) family accelerate GTP hydrolysis by the alpha subunits (G(alpha)) of G proteins, leading to rapid recovery of signaling cascades. Many different RGS proteins can accelerate GTP hydrolysis by an individual G(alpha), and GTP hydrolysis rates of different G(alpha)s can be enhanced by the same RGS protein. Consequently, the mechanisms for specificity in RGS regulation and the residues involved remain unclear. Using the evolutionary trace (ET) method, we have identified a cluster of residues in the RGS domain that includes the RGS-G(alpha) binding interface and extends to include additional functionally important residues on the surface. One of these is within helix alpha3, two are in alpha5, and three are in the loop connecting alpha5 and alpha6. A cluster of surface residues on G(alpha) previously identified by ET, and composed predominantly of residues from the switch III region and helix alpha3, is spatially contiguous with the ET-identified residues in the RGS domain. This cluster includes residues proposed to interact with the gamma subunit of G(talpha)'s effector, cGMP phosphodiesterase (PDEgamma). The proximity of these clusters suggests that they form part of an interface between the effector and the RGS-G(alpha) complex. Sequence variations in these residues correlate with PDEgamma effects on GTPase acceleration. Because ET identifies residues important for all members of a protein family, these residues likely form a general site for regulation of G protein-coupled signaling cascades, possibly by means of effector interactions.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2005

The Pseudomonas syringae effector AvrRpt2 cleaves its C-terminally acylated target, RIN4, from Arabidopsis membranes to block RPM1 activation.

Plant pathogenic Pseudomonas syringae deliver type III effector proteins into the host cell, where they function to manipulate host defense and metabolism to benefit the extracellular bacterial colony. The activity of these virulence factors can be monitored by plant disease resistance proteins deployed to "guard" the targeted host proteins. The Arabidopsis RIN4 protein is targeted by three different type III effectors. Specific manipulation of RIN4 by each of them leads to activation of either the RPM1 or RPS2 disease resistance proteins. The type III effector AvrRpt2 is a cysteine protease that is autoprocessed inside the host cell where it activates RPS2 by causing RIN4 disappearance. RIN4 contains two sites related to the AvrRpt2 cleavage site (RCS1 and RCS2). We demonstrate that AvrRpt2-dependent cleavage of RIN4 at RCS2 is functionally critical in vivo. This event leads to proteasome-mediated elimination of all but a membrane-embedded approximately 6.4-kDa C-terminal fragment of RIN4. One or more of three consecutive cysteines in this C-terminal fragment are required for RIN4 localization; these are likely to be palmitoylation and/or prenylation sites. AvrRpt2-dependent cleavage at RCS2, and release of the remainder of RIN4 from the membrane, consequently prevents RPM1 activation by AvrRpm1 or AvrB. RCS2 is contained within the smallest tested fragment of RIN4 that binds AvrB in vitro. Thus, at least two bacterial virulence factors target the same domain of RIN4, a approximately 30-aa plant-specific signature sequence found in a small Arabidopsis protein family that may be additional targets for these bacterial virulence factors.

Amino Acid Sequence↗