2.50
HDL Handle:
http://hdl.handle.net/10033/214070
Title:
Integrating signals from the T-cell receptor and the interleukin-2 receptor.
Authors:
Beyer, Tilo; Busse, Mandy; Hristov, Kroum; Gurbiel, Slavyana; Smida, Michal; Haus, Utz-Uwe; Ballerstein, Kathrin; Pfeuffer, Frank; Weismantel, Robert; Schraven, Burkhart; Lindquist, Jonathan A
Abstract:
T cells orchestrate the adaptive immune response, making them targets for immunotherapy. Although immunosuppressive therapies prevent disease progression, they also leave patients susceptible to opportunistic infections. To identify novel drug targets, we established a logical model describing T-cell receptor (TCR) signaling. However, to have a model that is able to predict new therapeutic approaches, the current drug targets must be included. Therefore, as a next step we generated the interleukin-2 receptor (IL-2R) signaling network and developed a tool to merge logical models. For IL-2R signaling, we show that STAT activation is independent of both Src- and PI3-kinases, while ERK activation depends upon both kinases and additionally requires novel PKCs. In addition, our merged model correctly predicted TCR-induced STAT activation. The combined network also allows information transfer from one receptor to add detail to another, thereby predicting that LAT mediates JNK activation in IL-2R signaling. In summary, the merged model not only enables us to unravel potential cross-talk, but it also suggests new experimental designs and provides a critical step towards designing strategies to reprogram T cells.
Affiliation:
Institute of Molecular and Clinical Immunology, Otto-von-Guericke University, Magdeburg, Germany.
Citation:
Integrating signals from the T-cell receptor and the interleukin-2 receptor. 2011, 7 (8):e1002121 PLoS Comput. Biol.
Journal:
PLoS computational biology
Issue Date:
Aug-2011
URI:
http://hdl.handle.net/10033/214070
DOI:
10.1371/journal.pcbi.1002121
PubMed ID:
21829342
Type:
Article
Language:
en
ISSN:
1553-7358
Appears in Collections:
publications of the department of immunocontrol (IMMK)

Full metadata record

DC FieldValueLanguage
dc.contributor.authorBeyer, Tiloen
dc.contributor.authorBusse, Mandyen
dc.contributor.authorHristov, Kroumen
dc.contributor.authorGurbiel, Slavyanaen
dc.contributor.authorSmida, Michalen
dc.contributor.authorHaus, Utz-Uween
dc.contributor.authorBallerstein, Kathrinen
dc.contributor.authorPfeuffer, Franken
dc.contributor.authorWeismantel, Roberten
dc.contributor.authorSchraven, Burkharten
dc.contributor.authorLindquist, Jonathan Aen
dc.date.accessioned2012-03-02T14:46:01Z-
dc.date.available2012-03-02T14:46:01Z-
dc.date.issued2011-08-
dc.identifier.citationIntegrating signals from the T-cell receptor and the interleukin-2 receptor. 2011, 7 (8):e1002121 PLoS Comput. Biol.en
dc.identifier.issn1553-7358-
dc.identifier.pmid21829342-
dc.identifier.doi10.1371/journal.pcbi.1002121-
dc.identifier.urihttp://hdl.handle.net/10033/214070-
dc.description.abstractT cells orchestrate the adaptive immune response, making them targets for immunotherapy. Although immunosuppressive therapies prevent disease progression, they also leave patients susceptible to opportunistic infections. To identify novel drug targets, we established a logical model describing T-cell receptor (TCR) signaling. However, to have a model that is able to predict new therapeutic approaches, the current drug targets must be included. Therefore, as a next step we generated the interleukin-2 receptor (IL-2R) signaling network and developed a tool to merge logical models. For IL-2R signaling, we show that STAT activation is independent of both Src- and PI3-kinases, while ERK activation depends upon both kinases and additionally requires novel PKCs. In addition, our merged model correctly predicted TCR-induced STAT activation. The combined network also allows information transfer from one receptor to add detail to another, thereby predicting that LAT mediates JNK activation in IL-2R signaling. In summary, the merged model not only enables us to unravel potential cross-talk, but it also suggests new experimental designs and provides a critical step towards designing strategies to reprogram T cells.en
dc.language.isoenen
dc.subject.meshCells, Cultureden
dc.subject.meshHumansen
dc.subject.meshModels, Biologicalen
dc.subject.meshPhosphatidylinositol 3-Kinasesen
dc.subject.meshProtein Kinase Cen
dc.subject.meshReceptor Cross-Talken
dc.subject.meshReceptors, Antigen, T-Cellen
dc.subject.meshReceptors, Interleukin-2en
dc.subject.meshReproducibility of Resultsen
dc.subject.meshSTAT Transcription Factorsen
dc.subject.meshSignal Transductionen
dc.subject.meshT-Lymphocytesen
dc.subject.meshsrc-Family Kinasesen
dc.titleIntegrating signals from the T-cell receptor and the interleukin-2 receptor.en
dc.typeArticleen
dc.contributor.departmentInstitute of Molecular and Clinical Immunology, Otto-von-Guericke University, Magdeburg, Germany.en
dc.identifier.journalPLoS computational biologyen

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