ArticleThe Journal of biological chemistry2012
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.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- ROCK1 promotes B cell differentiation and proteostasis under stress through the heme-regulated proteins, BACH2 and HRI.JCI insight · 2025Article
- DEF6(differentially exprehomolog) exacerbates pathological cardiac hypertrophy via RAC1.Cell death & disease · 2023Article
- Itk Promotes the Integration of TCR and CD28 Costimulation through Its Direct Substrates SLP-76 and Gads.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Human DEF6 deficiency underlies an immunodeficiency syndrome with systemic autoimmunity and aberrant CTLA-4 homeostasis.Nature communications · 2019Article
- Whole exome sequencing in three families segregating a pediatric case of sarcoidosis.BMC medical genomics · 2018Article
- Article
- Regulation of systemic autoimmunity and CD11cCellular immunology · 2017Review
- The mTORC1-4E-BP-eIF4E axis controls de novo Bcl6 protein synthesis in T cells and systemic autoimmunity.Nature communications · 2017Article
- Identification of a Novel Alternatively Spliced Form of Inflammatory Regulator SWAP-70-Like Adapter of T Cells.International journal of inflammation · 2017Article
- DEF6 expression in ovarian carcinoma correlates with poor patient survival.Diagnostic pathology · 2016Article
- Regulation of Effector Treg Cells in Murine Lupus.Arthritis & rheumatology (Hoboken, N.J.) · 2016Article
- Association of polyalanine and polyglutamine coiled coils mediates expansion disease-related protein aggregation and dysfunction.Human molecular genetics · 2014Article
- IBP regulates epithelial-to-mesenchymal transition and the motility of breast cancer cells via Rac1, RhoA and Cdc42 signaling pathways.Oncogene · 2014Article
- The switch-associated protein 70 (SWAP-70) bundles actin filaments and contributes to the regulation of F-actin dynamics.The Journal of biological chemistry · 2013Article
- Substrate recognition of PLCγ1 via a specific docking surface on Itk.Journal of molecular biology · 2013Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
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 Tyr(210) and Tyr(222). 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.
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Registered trials
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