The MAPK dual specific phosphatase (DUSP) proteins: A versatile wrestler in T cell functionality

Int Immunopharmacol. 2021 Sep:98:107906. doi: 10.1016/j.intimp.2021.107906. Epub 2021 Jun 28.

Abstract

The functional state of T cells is diverse and under dynamic control for adapting to the changes of microenvironment. Reversible protein phosphorylation represents an important post-translational modification that not only involves in the immediate early response of T cells, but also affects their functionality in the long run. Perturbation of global phosphorylation profile and/or phosphorylation of specific signaling nodes result in aberrant T cell activity. Dual specific phosphatases (DUSPs), which target MAPKs and beyond, have increasingly been emerged as a versatile regulator in T cell biology. Herein in this mini review, we sought to summarize and discuss the impact of DUSP proteins on the regulation of effector T cell activity, T cell polarization, regulatory T cell development and T cell senescence/exhaustion. Given the distinctive engagement of each DUSP member under various disease settings such as chronic infection, autoimmune disorders, cancer and age-related diseases, DUSP proteins likely hold the promise to become a druggable target other than the existing therapeutics that are predominantly by manipulating protein kinase activity.

Keywords: DUSPs; Effector T cell; Regulatory T cell; T cell senescence/exhaustion.

Publication types

  • Review

MeSH terms

  • Animals
  • Cellular Senescence / immunology
  • Dual-Specificity Phosphatases / metabolism*
  • Humans
  • Lymphocyte Activation
  • MAP Kinase Signaling System / immunology*
  • Phosphorylation / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • Dual-Specificity Phosphatases