PloS one, 2013-10, Vol.8 (10), p.e75200-e75200
2013
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Details
- Autor(en) / Beteiligte
- Titel
- The discovery of a reciprocal relationship between tyrosine-kinase signaling and cullin neddylation
- Ist Teil von
- PloS one, 2013-10, Vol.8 (10), p.e75200-e75200
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2013
- Quelle
- EZB-FREE-00999 freely available EZB journals
- Beschreibungen/Notizen
- While neddylation is known to activate cullin (CUL)-RING ubiquitin ligases (CRLs), its role in regulating T cell signaling is poorly understood. Using the investigational NEDD8 activating enzyme (NAE) inhibitor, MLN4924, we found that neddylation negatively regulates T cell receptor (TCR) signaling, as its inhibition increases IL-2 production, T cell proliferation and Treg development in vitro. We also discovered that loss of CUL neddylation occurs upon TCR signaling, and CRLs negatively regulate IL-2 production. Additionally, we found that tyrosine kinase signaling leads to CUL deneddylation in multiple cell types. These studies indicate that CUL neddylation is a global regulatory mechanism for tyrosine kinase signaling.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0075200Titel-ID: cdi_plos_journals_2037238807
- Format
- –
- Schlagworte
- Animals, B cells, Cell Death - physiology, Cell proliferation, Cells, Cultured, Cullin, Cullin Proteins - genetics, Cullin Proteins - metabolism, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Immunoblotting, Interleukin 2, Interleukin-2 - metabolism, Ligases, Lymphocytes T, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Phenols (Class of compounds), Protein-tyrosine kinase, Protein-Tyrosine Kinases - genetics, Protein-Tyrosine Kinases - metabolism, Regulatory mechanisms (biology), Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction - genetics, Signal Transduction - physiology, Signaling, T cell receptors, T cells, T-cell receptor, T-Lymphocytes, Regulatory - metabolism, Tyrosine, Ubiquitin