DRAK2 regulates myosin light chain phosphorylation in T cells

J Cell Sci. 2024 Nov 15;137(22):jcs261813. doi: 10.1242/jcs.261813. Epub 2024 Nov 20.

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.

Keywords: DRAK2; Microcluster; Migration; Myosin; STK17B; T cell.

MeSH terms

  • Actins / metabolism
  • Animals
  • Cell Movement
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myosin Light Chains* / metabolism
  • Phosphorylation
  • Protein Serine-Threonine Kinases* / genetics
  • Protein Serine-Threonine Kinases* / metabolism
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes* / immunology
  • T-Lymphocytes* / metabolism

Substances

  • Myosin Light Chains
  • Protein Serine-Threonine Kinases
  • Actins
  • Receptors, Antigen, T-Cell