Benjamin A Wilander, Tarsha L Harris, Alexandra H Mandarano, Cliff S Guy, Mollie S Prater, Shondra M Pruett-Miller, Stacey K Ogden, Maureen A McGargill
{"title":"DRAK2 regulates myosin light chain phosphorylation in T cells.","authors":"Benjamin A Wilander, Tarsha L Harris, Alexandra H Mandarano, Cliff S Guy, Mollie S Prater, Shondra M Pruett-Miller, Stacey K Ogden, Maureen A McGargill","doi":"10.1242/jcs.261813","DOIUrl":null,"url":null,"abstract":"<p><p>Death-associated protein kinase-related apoptosis-inducing kinase-2 (DRAK2; also known as STK17B) is a serine/threonine kinase expressed in T cells. Drak2-deficient (Drak2-/-) mice respond effectively to tumors and pathogens while displaying resistance to T cell-mediated autoimmune disease. However, the molecular mechanisms by which DRAK2 impacts T cell function remain unclear. Gaining further insight into the function of DRAK2 in T cells will shed light on differentially regulated pathways in autoreactive and pathogen-specific T cells, which is crucial for improving autoimmune therapies. Here, we demonstrate that DRAK2 contributes to activation of myosin light chain (MLC2, encoded by Myl2) in both murine and human T cells. In the absence of Drak2, the amount of polymerized actin was decreased, suggesting that DRAK2 modulates actomyosin dynamics. We further show that myosin-dependent T cell functions, such as migration, T cell receptor microcluster accumulation, and conjugation to antigen presenting cells are decreased in the absence of Drak2. These findings reveal that DRAK2 plays an important role in regulating MLC activation within T cells.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11607690/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of cell science","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1242/jcs.261813","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/20 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Death-associated protein kinase-related apoptosis-inducing kinase-2 (DRAK2; also known as STK17B) is a serine/threonine kinase expressed in T cells. Drak2-deficient (Drak2-/-) mice respond effectively to tumors and pathogens while displaying resistance to T cell-mediated autoimmune disease. However, the molecular mechanisms by which DRAK2 impacts T cell function remain unclear. Gaining further insight into the function of DRAK2 in T cells will shed light on differentially regulated pathways in autoreactive and pathogen-specific T cells, which is crucial for improving autoimmune therapies. Here, we demonstrate that DRAK2 contributes to activation of myosin light chain (MLC2, encoded by Myl2) in both murine and human T cells. In the absence of Drak2, the amount of polymerized actin was decreased, suggesting that DRAK2 modulates actomyosin dynamics. We further show that myosin-dependent T cell functions, such as migration, T cell receptor microcluster accumulation, and conjugation to antigen presenting cells are decreased in the absence of Drak2. These findings reveal that DRAK2 plays an important role in regulating MLC activation within T cells.
死亡相关蛋白激酶相关凋亡诱导激酶-2(DRAK2或STK17B)是一种在T细胞中表达的丝氨酸/苏氨酸激酶。Drak2缺陷(Drak2-/-)小鼠对肿瘤和病原体反应有效,同时对T细胞介导的自身免疫性疾病表现出抵抗力。然而,DRAK2影响T细胞功能的分子机制仍不清楚。进一步了解 DRAK2 在 T 细胞中的功能将有助于了解自体反应性 T 细胞和病原体特异性 T 细胞的不同调控途径,这对改善自身免疫疗法至关重要。在这里,我们证明了DRAK2有助于激活鼠和人T细胞中的肌球蛋白轻链(MLC)。在缺少 Drak2 的情况下,聚合肌动蛋白的量减少,这表明 DRAK2 可调节肌动蛋白的动力学。我们进一步发现,在缺少 Drak2 的情况下,肌动蛋白依赖的 T 细胞功能,如迁移、T 细胞受体微簇聚集和与抗原呈递细胞的结合等,都会降低。这些发现揭示了 DRAK2 在调节 T 细胞内 MLC 的活化方面发挥着重要作用。