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.
Footnotes
Author contributions
Conceptualization: B.A.W., T.L.H., M.A.M.; Methodology: B.A.W., C.S.G., S.M.P.-M., M.A.M.; Validation: B.A.W., S.M.P.-M., M.A.M.; Formal analysis: B.A.W., A.H.M., M.A.M.; Investigation: B.A.W., T.L.H., A.H.M., C.S.G., M.S.P., S.M.P.-M., M.A.M.; Data curation: B.A.W.; Writing - original draft: B.A.W., M.A.M.; Writing - review & editing: B.A.W., A.H.M., S.M.P.-M., S.K.O., M.A.M.; Visualization: B.A.W., M.A.M.; Supervision: S.K.O., M.A.M.; Project administration: M.A.M.; Funding acquisition: B.A.W.
Funding
Research reported in this publication was supported by the National Institute of Allergy and Infectious Disease of the National Institutes of Health under award number 1F31AI172380-01A1 (B.A.W.), by the National Cancer Institute grant P30 CA021765 (S.M.P), and the American Lebanese Syrian Associated Charities (M.A.M.). Deposited in PMC for release after 12 months.
Data availability
All relevant data can be found within the article and its supplementary information.
