Lck Mediates Signal Transmission from CD59 to the TCR/CD3 Pathway in Jurkat T Cells
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{"title"=>"Lck mediates signal transmission from CD59 to the TCR/CD3 pathway in Jurkat T cells", "type"=>"journal", "authors"=>[{"first_name"=>"Anna M.", "last_name"=>"Lipp", "scopus_author_id"=>"37037848700"}, {"first_name"=>"Kata", "last_name"=>"Juhasz", "scopus_author_id"=>"57200716919"}, {"first_name"=>"Christian", "last_name"=>"Paar", "scopus_author_id"=>"8421487900"}, {"first_name"=>"Christoph", "last_name"=>"Ogris", "scopus_author_id"=>"55992088200"}, {"first_name"=>"Paul", "last_name"=>"Eckerstorfer", "scopus_author_id"=>"26040641300"}, {"first_name"=>"Roland", "last_name"=>"Thuenauer", "scopus_author_id"=>"50562203500"}, {"first_name"=>"Jan", "last_name"=>"Hesse", "scopus_author_id"=>"7004408526"}, {"first_name"=>"Benedikt", "last_name"=>"Nimmervoll", "scopus_author_id"=>"55003082300"}, {"first_name"=>"Hannes", "last_name"=>"Stockinger", "scopus_author_id"=>"7007051269"}, {"first_name"=>"Gerhard J.", "last_name"=>"Schütz", "scopus_author_id"=>"7102515765"}, {"first_name"=>"Ulrich", "last_name"=>"Bodenhofer", "scopus_author_id"=>"6602978986"}, {"first_name"=>"Zsolt", "last_name"=>"Balogi", "scopus_author_id"=>"6508296510"}, {"first_name"=>"Alois", "last_name"=>"Sonnleitner", "scopus_author_id"=>"6602704491"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84898635046", "pui"=>"372838169", "doi"=>"10.1371/journal.pone.0085934", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "sgr"=>"84898635046", "pmid"=>"24454946"}, "id"=>"b9db6c35-6607-3144-9e72-858afed7b952", "abstract"=>"The glycosylphosphatidylinositol (GPI)-anchored molecule CD59 has been implicated in the modulation of T cell responses, but the underlying molecular mechanism of CD59 influencing T cell signaling remained unclear. Here we analyzed Jurkat T cells stimulated via anti-CD3epsilon- or anti-CD59-coated surfaces, using time-resolved single-cell Ca(2+) imaging as a read-out for stimulation. This analysis revealed a heterogeneous Ca(2+) response of the cell population in a stimulus-dependent manner. Further analysis of T cell receptor (TCR)/CD3 deficient or overexpressing cells showed that CD59-mediated signaling is strongly dependent on TCR/CD3 surface expression. In protein co-patterning and fluorescence recovery after photobleaching experiments no direct physical interaction was observed between CD59 and CD3 at the plasma membrane upon anti-CD59 stimulation. However, siRNA-mediated protein knock-downs of downstream signaling molecules revealed that the Src family kinase Lck and the adaptor molecule linker of activated T cells (LAT) are essential for both signaling pathways. Furthermore, flow cytometry measurements showed that knock-down of Lck accelerates CD3 re-expression at the cell surface after anti-CD59 stimulation similar to what has been observed upon direct TCR/CD3 stimulation. Finally, physically linking Lck to CD3zeta completely abolished CD59-triggered Ca(2+) signaling, while signaling was still functional upon direct TCR/CD3 stimulation. Altogether, we demonstrate that Lck mediates signal transmission from CD59 to the TCR/CD3 pathway in Jurkat T cells, and propose that CD59 may act via Lck to modulate T cell responses.", "link"=>"http://www.mendeley.com/research/lck-mediates-signal-transmission-cd59-tcrcd3-pathway-jurkat-t-cells", "reader_count"=>29, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Researcher"=>9, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>6, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>1, "Professor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Researcher"=>9, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>6, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>1, "Professor"=>4}, "reader_count_by_subject_area"=>{"Engineering"=>3, "Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>12, "Physics and Astronomy"=>1, "Chemistry"=>2, "Computer Science"=>1, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>3}, "Chemistry"=>{"Chemistry"=>2}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>12}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>3}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1347343"], "description"=>"<p>Jurkat cells (WT) were loaded with Indo-1/AM followed by stimulation with anti-CD3-, anti-CD59-, or anti-CD71-coated surfaces. Individual Ca<sup>2+</sup> time traces were measured for 200 s after identification of initial cell-surface contact as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0085934#pone-0085934-g001\" target=\"_blank\">Figure 1S</a>. (A) Box plots of individual Ca<sup>2+</sup> time traces generated by analysis of the whole cell population upon anti-CD3, anti-CD59, and anti-CD71 stimulation (black line  =  median, grey area  = 50% of Ca<sup>2+</sup> time traces, dotted lines  =  75% of Ca<sup>2+</sup> time traces). (B) Individual Ca<sup>2+</sup> time traces from single-cell measurements were grouped into 11 clusters by affinity propagation clustering as described in Materials and Methods. Each plot shows the respective Ca<sup>2+</sup> time traces for a cluster, an exemplar trace for each cluster is shown in black. Clusters representing Ca<sup>2+</sup> release patterns are framed in black. (C) Stimulus-dependent cluster distribution upon anti-CD3, anti-CD59, and anti-CD71 stimulation in WT cells is shown by stacked bar plots. Each color represents the percentage of a certain Ca<sup>2+</sup> time trace cluster in the cell population. Clusters representing Ca<sup>2+</sup> release patterns are framed in black (88.5±4.9%, 31.8±12.0%, and 5.5±5.3% for anti-CD3, anti-CD59, and anti-CD71 stimulation, respectively). Mean values from at least three independent experiments, each with three technical replicates, are shown (n ≥ 249 per stimulatory condition). (D) CD3ε and CD59 surface expression levels in WT cells. WT cells were surface stained with Alexa Fluor 647-conjugated anti-CD3ε and FITC-conjugated anti-CD59 or isotype controls and analyzed by flow cytometry. Live cells were gated based on the Forward Scatter and Side Scatter profiles and propidium iodide exclusion. A representative dot plot of four technical replicates is shown.</p>", "links"=>[], "tags"=>["immunology", "Immune cells", "t cells", "Molecular cell biology", "Cellular types", "Jurkat Cells", "Signal transduction", "Membrane receptor signaling", "Immunologic receptor signaling", "Signaling cascades", "TCR signaling cascade", "Signaling in cellular processes", "Calcium signaling", "Signaling pathways", "Calcium-mediated signal transduction", "Mechanisms of signal transduction", "Clinical immunology", "differential", "heterogeneity", "anti-cd3", "anti-cd59"], "article_id"=>901033, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Anna M. Lipp", "Kata Juhasz", "Christian Paar", "Christoph Ogris", "Paul Eckerstorfer", "Roland Thuenauer", "Jan Hesse", "Benedikt Nimmervoll", "Hannes Stockinger", "Gerhard J. Schütz", "Ulrich Bodenhofer", "Zsolt Balogi", "Alois Sonnleitner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0085934.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Single_cell_Ca_2_measurements_reveal_differential_heterogeneity_upon_anti_CD3_and_anti_CD59_stimulation_/901033", "title"=>"Single-cell Ca<sup>2+</sup> measurements reveal differential heterogeneity upon anti-CD3 and anti-CD59 stimulation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-15 02:49:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1347345"], "description"=>"<p>(A) Cluster distribution of Ca<sup>2+</sup> time traces in WT and TCR<sup>high</sup> cells is shown upon anti-CD3 and anti-CD59 stimulation. Each color represents the percentage of a certain Ca<sup>2+</sup> time trace cluster in the cell population. Clusters representing Ca<sup>2+</sup> release patterns are framed in black (91.4±2.1% and 92.9±3.9% upon anti-CD3 stimulation, 34.4±16.3% and 72.0±16.6% upon anti-CD59 stimulation in WT and TCR<sup>high</sup> cells, respectively). Mean values from two independent experiments, each with three technical replicates are shown (n ≥ 167 per cell type and condition). (B) Cluster distribution of Ca<sup>2+</sup> time traces in WT, TCR<sup>-</sup>, and cells expressing CD8-ζ fusion protein is shown upon anti-CD3 and anti-CD59 stimulation. Each color represents the percentage of a certain Ca<sup>2+</sup> time trace cluster in the cell population. Clusters representing Ca<sup>2+</sup> release patterns are framed in black (90.1±1.4%, 1.9±0.7% and 7.4±2.3% upon anti-CD3 stimulation, 25.2±6.8%, 1.6±0.4% and 13.4±1.6% upon anti-CD59 stimulation for WT, TCR<sup>-</sup>, and CD8-ζ cells, respectively). Mean values from four independent experiments, each with three technical replicates, are shown (n ≥ 343 per cell type and condition). Multiple comparison tests for the fractions showing Ca<sup>2+</sup> release patterns in (A) and (B) were assessed by one-way ANOVA, significances are shown where applicable, * p < 0.05, ** p < 0.01, *** p < 0.001.</p>", "links"=>[], "tags"=>["immunology", "Immune cells", "t cells", "Molecular cell biology", "Cellular types", "Jurkat Cells", "Signal transduction", "Membrane receptor signaling", "Immunologic receptor signaling", "Signaling cascades", "TCR signaling cascade", "Signaling in cellular processes", "Calcium signaling", "Signaling pathways", "Calcium-mediated signal transduction", "Mechanisms of signal transduction", "Clinical immunology", "requires"], "article_id"=>901035, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Anna M. Lipp", "Kata Juhasz", "Christian Paar", "Christoph Ogris", "Paul Eckerstorfer", "Roland Thuenauer", "Jan Hesse", "Benedikt Nimmervoll", "Hannes Stockinger", "Gerhard J. Schütz", "Ulrich Bodenhofer", "Zsolt Balogi", "Alois Sonnleitner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0085934.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CD59_mediated_Ca_2_signaling_requires_CD3_950_expression_/901035", "title"=>"CD59-mediated Ca<sup>2+</sup> signaling requires CD3ζ expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-15 02:49:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1347351"], "description"=>"<p>(A) Distribution of CD3ζ-EYFP in Jurkat cells on Ab-patterned surfaces. Non-Ab-coated BSA-Cy5 spots are shown as a control in the left column. In the right column, TIRF microscopy images of Jurkat cells expressing CD3ζ-EYFP are shown on (a) anti-CD3ε, (b) anti-CD59, or (c) anti-CD71 grids (scale bars  =  10 µm). (B) FRAP measurements of CD3ζ-EYFP in Jurkat cells. After acquiring pre-bleach images, CD3ζ-EYFP was bleached in a defined area (red rectangle) at the bottom of the cell attached to anti-CD3ε-, anti-CD59-, or anti-CD71-coated surfaces. Recovering fluorescence intensity in the area was imaged at indicated time points (scale bars  =  5 µm). (C) Fluorescence recovery curves of CD3ζ-EYFP in cells plated on anti-CD3ε-, anti-CD59-, or anti-CD71-coated surfaces (mean ±SD). (D) Immobile fractions of CD3ζ-EYFP calculated from fluorescence recovery curves. Representative data of two separate experiments are shown (mean ±SD, n≥3). Multiple comparison tests were assessed by one-way ANOVA, significances are shown where applicable, ** p<0.01.</p>", "links"=>[], "tags"=>["immunology", "Immune cells", "t cells", "Molecular cell biology", "Cellular types", "Jurkat Cells", "Signal transduction", "Membrane receptor signaling", "Immunologic receptor signaling", "Signaling cascades", "TCR signaling cascade", "Signaling in cellular processes", "Calcium signaling", "Signaling pathways", "Calcium-mediated signal transduction", "Mechanisms of signal transduction", "Clinical immunology", "static", "cd59", "cd3", "anti-cd59"], "article_id"=>901041, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Anna M. Lipp", "Kata Juhasz", "Christian Paar", "Christoph Ogris", "Paul Eckerstorfer", "Roland Thuenauer", "Jan Hesse", "Benedikt Nimmervoll", "Hannes Stockinger", "Gerhard J. Schütz", "Ulrich Bodenhofer", "Zsolt Balogi", "Alois Sonnleitner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0085934.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Neither_static_nor_dynamic_interaction_between_CD59_and_CD3_at_the_cell_surface_is_visible_upon_anti_CD59_stimulation_/901041", "title"=>"Neither static nor dynamic interaction between CD59 and CD3 at the cell surface is visible upon anti-CD59 stimulation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-15 02:49:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1347352"], "description"=>"<p>Cluster distribution of Ca<sup>2+</sup> time traces in differently treated cells upon anti-CD3 and anti-CD59 stimulation. Each color represents the percentage of a certain Ca<sup>2+</sup> time trace cluster in the cell population. (A) Ca<sup>2+</sup> measurements were performed with WT cells transiently transfected with negative control siRNA (siNeg), Lck-specific siRNA (siLck), WT cells treated with 10 µM PP2 (PP2), and Lck-deficient J.CaM1.6 cells. Clusters representing Ca<sup>2+</sup> release patterns are framed in black (89.4±10.1%, 76.5±10.4%, 28.3±39.1%, and 23.4±9.9% upon anti-CD3 stimulation, 36.9±13.2%, 12.7±6.1%, 2.6±2.0%, and 1.2±1.2% upon anti-CD59 stimulation for siNeg, siLck, PP2-treated, and J.CaM1.6 cells, respectively). Mean values from at least two independent experiments, each with three technical replicates, are shown (n ≥ 204 per cell type and condition). (B) Cluster analysis of Ca<sup>2+</sup> time traces in WT cells transiently transfected with negative control siRNA (siNeg), LAT-specific siRNA (siLAT), and LAT-deficient J.CaM2.5 cells. Clusters representing Ca<sup>2+</sup> release patterns are framed in black (89.4±10.1%, 73.5±5.8%, and 3.0±2.3% upon anti-CD3 stimulation, 36.9±13.2%, 13.0±6.6%, and 1.7±1.6% upon anti-CD59 stimulation for siNeg, siLAT, and J.CaM2.5 cells, respectively). Mean values from at least three independent experiments, each with three technical replicates, are shown (n ≥ 208 per cell type and condition). Multiple comparison tests for the fractions showing Ca<sup>2+</sup> release patterns in (A) and (B) were assessed by one-way ANOVA, significances are shown where applicable, ** p < 0.01, *** p < 0.001. (C) Knock-down of target proteins was tested by Western blotting. 48 h after transfection cell lysates from siRNA treated cells were probed with anti-Lck, anti-LAT, and anti-β-actin. J.CaM1.6 cells, J.CaM2.5 cells, and WT cells served as controls.</p>", "links"=>[], "tags"=>["immunology", "Immune cells", "t cells", "Molecular cell biology", "Cellular types", "Jurkat Cells", "Signal transduction", "Membrane receptor signaling", "Immunologic receptor signaling", "Signaling cascades", "TCR signaling cascade", "Signaling in cellular processes", "Calcium signaling", "Signaling pathways", "Calcium-mediated signal transduction", "Mechanisms of signal transduction", "Clinical immunology", "cd59-mediated", "lck"], "article_id"=>901042, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Anna M. Lipp", "Kata Juhasz", "Christian Paar", "Christoph Ogris", "Paul Eckerstorfer", "Roland Thuenauer", "Jan Hesse", "Benedikt Nimmervoll", "Hannes Stockinger", "Gerhard J. Schütz", "Ulrich Bodenhofer", "Zsolt Balogi", "Alois Sonnleitner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0085934.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TCR_CD3_and_CD59_mediated_Ca_2_signaling_are_dependent_on_Lck_and_LAT_/901042", "title"=>"TCR/CD3- and CD59-mediated Ca<sup>2+</sup> signaling are dependent on Lck and LAT.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-15 02:49:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1347353"], "description"=>"<p>WT cells were transfected with negative control siRNA (siNeg) or Lck-specific siRNA (siLck) and experiments were performed 48 h after transfection. (A) Testing of Lck knock-down efficiency. Cell lysates were probed by Western blotting for Lck expression and β-actin as a control. (B) Efficiency of Lck knock-down tested by ensemble Ca<sup>2+</sup> measurements. siLck and siNeg cells were loaded with Indo-1/AM. Cells were incubated with anti-CD59 mAb or anti-IgG2a for 5 min at 37 °C. For antibody cross-linking, goat anti-mouse F(ab’)<sub>2</sub> was added to samples and Ca<sup>2+</sup> mobilization of the whole cell population was measured by a microplate reader. For testing TCR surface expression levels, cells were stimulated with anti-CD59 or anti-IgG2a, as isotype control, followed by incubation with goat anti-mouse F(ab’)<sub>2</sub> for (C) 1 h or (D) 15 h at 37°C. Cells were surface stained at 4 °C with FITC-conjugated anti-CD3ε or isotype control and analyzed by flow cytometry. Live cells were gated based on the Forward Scatter and Side Scatter profiles and propidium iodide exclusion. Fluorescence values displayed are isotype control corrected. Representative results of two separate experiments are shown (mean ±SD, n = 4). Multiple comparison tests were assessed by one-way ANOVA, significances are shown where applicable, ***p < 0.001.</p>", "links"=>[], "tags"=>["immunology", "Immune cells", "t cells", "Molecular cell biology", "Cellular types", "Jurkat Cells", "Signal transduction", "Membrane receptor signaling", "Immunologic receptor signaling", "Signaling cascades", "TCR signaling cascade", "Signaling in cellular processes", "Calcium signaling", "Signaling pathways", "Calcium-mediated signal transduction", "Mechanisms of signal transduction", "Clinical immunology", "anti-cd59", "stimulation", "cd3"], "article_id"=>901043, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Anna M. Lipp", "Kata Juhasz", "Christian Paar", "Christoph Ogris", "Paul Eckerstorfer", "Roland Thuenauer", "Jan Hesse", "Benedikt Nimmervoll", "Hannes Stockinger", "Gerhard J. Schütz", "Ulrich Bodenhofer", "Zsolt Balogi", "Alois Sonnleitner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0085934.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Lck_expression_and_anti_CD59_stimulation_influence_CD3_surface_expression_/901043", "title"=>"Lck expression and anti-CD59 stimulation influence CD3 surface expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-15 02:49:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1347354"], "description"=>"<p>(A) Lck expression levels in WT cells, J.CaM1.6 cells and J.CaM1.6 cells expressing mEGFP-tagged Lck fused to CD3ζ (CD3ζ-Lck) were tested by Western blotting, the same blot was reprobed using anti-β-actin as a control. (B) Plasma membrane localization of CD3ζ-Lck-mEGFP in J.CaM1.6 cells was imaged by fluorescence microscopy. CD3ζ-Lck-mEGFP fluorescence and a bright field (BF) image of a transfected J.CaM1.6 cell are shown (scale bars  =  10 µm). (C) Cluster distribution of Ca<sup>2+</sup> time traces in Lck-deficient J.CaM1.6 cells and J.CaM1.6 cells stably expressing mEGFP-tagged Lck fused to CD3ζ (CD3ζ-Lck) is shown upon anti-CD3 or anti-CD59 stimulation. Each color represents the percentage of a certain Ca<sup>2+</sup> time trace cluster in the cell population. Clusters representing Ca<sup>2+</sup> release patterns are framed in black (35.7±4.9% and 71.8±2.3% upon anti-CD3 stimulation, 1.4±2.3% and 1.0±1.3% upon anti-CD59 stimulation for J.CaM1.6 and CD3ζ-Lck cells, respectively). Mean values from three independent experiments, each with three technical replicates, are shown (n ≥ 323 per cell type and condition). Multiple comparison tests for the fractions showing Ca<sup>2+</sup> release patterns were assessed by one-way ANOVA, significances are shown where applicable, ***p < 0.001.</p>", "links"=>[], "tags"=>["immunology", "Immune cells", "t cells", "Molecular cell biology", "Cellular types", "Jurkat Cells", "Signal transduction", "Membrane receptor signaling", "Immunologic receptor signaling", "Signaling cascades", "TCR signaling cascade", "Signaling in cellular processes", "Calcium signaling", "Signaling pathways", "Calcium-mediated signal transduction", "Mechanisms of signal transduction", "Clinical immunology", "lck", "forced", "facilitates", "cd59-mediated"], "article_id"=>901044, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Anna M. Lipp", "Kata Juhasz", "Christian Paar", "Christoph Ogris", "Paul Eckerstorfer", "Roland Thuenauer", "Jan Hesse", "Benedikt Nimmervoll", "Hannes Stockinger", "Gerhard J. Schütz", "Ulrich Bodenhofer", "Zsolt Balogi", "Alois Sonnleitner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0085934.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Reconstitution_of_Lck_by_forced_interaction_of_CD3_and_Lck_facilitates_TCR_CD3_but_not_CD59_mediated_Ca_2_signaling_/901044", "title"=>"Reconstitution of Lck by forced interaction of CD3ζ and Lck facilitates TCR/CD3- but not CD59-mediated Ca<sup>2+</sup> signaling.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-15 02:49:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1347363", "https://ndownloader.figshare.com/files/1347364", "https://ndownloader.figshare.com/files/1347365", "https://ndownloader.figshare.com/files/1347366", "https://ndownloader.figshare.com/files/1347367"], "description"=>"<div><p>The glycosylphosphatidylinositol (GPI)-anchored molecule CD59 has been implicated in the modulation of T cell responses, but the underlying molecular mechanism of CD59 influencing T cell signaling remained unclear. Here we analyzed Jurkat T cells stimulated via anti-CD3ε- or anti-CD59-coated surfaces, using time-resolved single-cell Ca<sup>2+</sup> imaging as a read-out for stimulation. This analysis revealed a heterogeneous Ca<sup>2+</sup> response of the cell population in a stimulus-dependent manner. Further analysis of T cell receptor (TCR)/CD3 deficient or overexpressing cells showed that CD59-mediated signaling is strongly dependent on TCR/CD3 surface expression. In protein co-patterning and fluorescence recovery after photobleaching experiments no direct physical interaction was observed between CD59 and CD3 at the plasma membrane upon anti-CD59 stimulation. However, siRNA-mediated protein knock-downs of downstream signaling molecules revealed that the Src family kinase Lck and the adaptor molecule linker of activated T cells (LAT) are essential for both signaling pathways. Furthermore, flow cytometry measurements showed that knock-down of Lck accelerates CD3 re-expression at the cell surface after anti-CD59 stimulation similar to what has been observed upon direct TCR/CD3 stimulation. Finally, physically linking Lck to CD3ζ completely abolished CD59-triggered Ca<sup>2+</sup> signaling, while signaling was still functional upon direct TCR/CD3 stimulation. Altogether, we demonstrate that Lck mediates signal transmission from CD59 to the TCR/CD3 pathway in Jurkat T cells, and propose that CD59 may act via Lck to modulate T cell responses.</p></div>", "links"=>[], "tags"=>["immunology", "Immune cells", "t cells", "Molecular cell biology", "Cellular types", "Jurkat Cells", "Signal transduction", "Membrane receptor signaling", "Immunologic receptor signaling", "Signaling cascades", "TCR signaling cascade", "Signaling in cellular processes", "Calcium signaling", "Signaling pathways", "Calcium-mediated signal transduction", "Mechanisms of signal transduction", "Clinical immunology", "mediates", "cd59", "pathway", "jurkat"], "article_id"=>901049, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Anna M. Lipp", "Kata Juhasz", "Christian Paar", "Christoph Ogris", "Paul Eckerstorfer", "Roland Thuenauer", "Jan Hesse", "Benedikt Nimmervoll", "Hannes Stockinger", "Gerhard J. Schütz", "Ulrich Bodenhofer", "Zsolt Balogi", "Alois Sonnleitner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0085934.s001", "https://dx.doi.org/10.1371/journal.pone.0085934.s002", "https://dx.doi.org/10.1371/journal.pone.0085934.s003", "https://dx.doi.org/10.1371/journal.pone.0085934.s004", "https://dx.doi.org/10.1371/journal.pone.0085934.s005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Lck_Mediates_Signal_Transmission_from_CD59_to_the_TCR_CD3_Pathway_in_Jurkat_T_Cells_/901049", "title"=>"Lck Mediates Signal Transmission from CD59 to the TCR/CD3 Pathway in Jurkat T Cells", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-01-15 02:49:27"}

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Relative Metric

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