DEF6, a novel substrate for the tec kinase ITK, contains a glutamine-rich aggregation-prone region and forms cytoplasmic granules that co-localize with P-bodies
Localization of DEF6 (SLAT/IBP), a Rho-family guanine nucleotide exchange factor, to the center of the immune synapse is dependent upon ITK, a Tec-family kinase that regulates the spatiotemporal organization of components of T cell signaling pathways and Cdc42-dependent actin polymerization. Here we...
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| author | Hey, Fiona Czyzewicz, Nathan Jones, Peter Sablitzky, Fred |
| author_facet | Hey, Fiona Czyzewicz, Nathan Jones, Peter Sablitzky, Fred |
| author_sort | Hey, Fiona |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Localization of DEF6 (SLAT/IBP), a Rho-family guanine nucleotide exchange factor, to the center of the immune synapse is dependent upon ITK, a Tec-family kinase that regulates the spatiotemporal organization of components of T cell signaling pathways and Cdc42-dependent actin polymerization. Here we demonstrate that ITK both interacts with DEF6 and phosphorylates DEF6 at tyrosine residues Tyr210 and Tyr222. Expression of a GFP-tagged Y210E-Y222E phosphomimic resulted in the formation of DEF6 cytoplasmic granules that co-localized with decapping enzyme 1 (DCP1), a marker of P-bodies; sites of mRNA degradation. Similarly treatment of cells with puromycin or sodium arsenite, reagents that arrest translation, also resulted in the accumulation of DEF6 in cytoplasmic granules. Bioinformatics analysis identified a glutamine-rich, heptad-repeat region; a feature of aggregating proteins, within the C-terminal region of DEF6 with the potential to promote granule formation through a phosphorylation-dependent unmasking of this region. These data suggest that in addition to its role as a GEF, DEF6 may also function in regulating mRNA translation. |
| first_indexed | 2025-11-14T18:20:06Z |
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| id | nottingham-2918 |
| institution | University of Nottingham Malaysia Campus |
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| last_indexed | 2025-11-14T18:20:06Z |
| publisher | American Society for Biochemistry and Molecular Biology |
| recordtype | eprints |
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| spelling | nottingham-29182020-05-04T20:34:37Z https://eprints.nottingham.ac.uk/2918/ DEF6, a novel substrate for the tec kinase ITK, contains a glutamine-rich aggregation-prone region and forms cytoplasmic granules that co-localize with P-bodies Hey, Fiona Czyzewicz, Nathan Jones, Peter Sablitzky, Fred Localization of DEF6 (SLAT/IBP), a Rho-family guanine nucleotide exchange factor, to the center of the immune synapse is dependent upon ITK, a Tec-family kinase that regulates the spatiotemporal organization of components of T cell signaling pathways and Cdc42-dependent actin polymerization. Here we demonstrate that ITK both interacts with DEF6 and phosphorylates DEF6 at tyrosine residues Tyr210 and Tyr222. Expression of a GFP-tagged Y210E-Y222E phosphomimic resulted in the formation of DEF6 cytoplasmic granules that co-localized with decapping enzyme 1 (DCP1), a marker of P-bodies; sites of mRNA degradation. Similarly treatment of cells with puromycin or sodium arsenite, reagents that arrest translation, also resulted in the accumulation of DEF6 in cytoplasmic granules. Bioinformatics analysis identified a glutamine-rich, heptad-repeat region; a feature of aggregating proteins, within the C-terminal region of DEF6 with the potential to promote granule formation through a phosphorylation-dependent unmasking of this region. These data suggest that in addition to its role as a GEF, DEF6 may also function in regulating mRNA translation. American Society for Biochemistry and Molecular Biology Article PeerReviewed Hey, Fiona, Czyzewicz, Nathan, Jones, Peter and Sablitzky, Fred DEF6, a novel substrate for the tec kinase ITK, contains a glutamine-rich aggregation-prone region and forms cytoplasmic granules that co-localize with P-bodies. Journal of Biological Chemistry, 287 (37). pp. 31073-31084. ISSN 0021-9258 Cell Biology Guanine Nucleotide Exchange Factor (GEF) P-body Signal Transduction T-cell Receptor http://www.jbc.org/content/287/37/31073.long doi:10.1074/jbc.M112.346767 doi:10.1074/jbc.M112.346767 |
| spellingShingle | Cell Biology Guanine Nucleotide Exchange Factor (GEF) P-body Signal Transduction T-cell Receptor Hey, Fiona Czyzewicz, Nathan Jones, Peter Sablitzky, Fred DEF6, a novel substrate for the tec kinase ITK, contains a glutamine-rich aggregation-prone region and forms cytoplasmic granules that co-localize with P-bodies |
| title | DEF6, a novel substrate for the tec kinase ITK, contains a glutamine-rich aggregation-prone region and forms cytoplasmic granules that co-localize with P-bodies |
| title_full | DEF6, a novel substrate for the tec kinase ITK, contains a glutamine-rich aggregation-prone region and forms cytoplasmic granules that co-localize with P-bodies |
| title_fullStr | DEF6, a novel substrate for the tec kinase ITK, contains a glutamine-rich aggregation-prone region and forms cytoplasmic granules that co-localize with P-bodies |
| title_full_unstemmed | DEF6, a novel substrate for the tec kinase ITK, contains a glutamine-rich aggregation-prone region and forms cytoplasmic granules that co-localize with P-bodies |
| title_short | DEF6, a novel substrate for the tec kinase ITK, contains a glutamine-rich aggregation-prone region and forms cytoplasmic granules that co-localize with P-bodies |
| title_sort | def6, a novel substrate for the tec kinase itk, contains a glutamine-rich aggregation-prone region and forms cytoplasmic granules that co-localize with p-bodies |
| topic | Cell Biology Guanine Nucleotide Exchange Factor (GEF) P-body Signal Transduction T-cell Receptor |
| url | https://eprints.nottingham.ac.uk/2918/ https://eprints.nottingham.ac.uk/2918/ https://eprints.nottingham.ac.uk/2918/ |