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Dok-4 is a novel negative regulator of T cell activation

Audrey Gérard1, Marguerite Ghiotto, Camille Fos

  • 1Unité 891, Institut National de la Santé et de la Recherche Médicale, Centre de Recherche en Cancérologie de Marseille, Marseille, France.

Journal of Immunology (Baltimore, Md. : 1950)
|June 5, 2009
PubMed

Insights

Dok-4, a novel adaptor protein, negatively regulates T cell activation. It is phosphorylated upon T cell receptor engagement and inhibits ERK phosphorylation, IL-2 production, and T cell proliferation.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Dok-4 is a newly identified member of the Dok family of adaptor proteins.
  • Dok-1 and Dok-2 are known negative regulators in T cells, but Dok-4's function is unknown.
  • Dok-4 is expressed in T cells.

Purpose of the Study:

  • To investigate the function of Dok-4 in T cells.
  • To determine Dok-4's role in T cell activation and signaling.

Main Methods:

  • TCR engagement and T cell stimulation.
  • Phosphorylation and subcellular localization studies of Dok-4.
  • Loss-of-function experiments using RNA interference.
  • Analysis of ERK phosphorylation, IL-2 promoter activity, and T cell proliferation.
  • Exogenous expression of wild-type Dok-4 and its domains.

Main Results:

  • Dok-4 is phosphorylated and translocates to the immunological synapse upon TCR engagement.
  • Dok-4 acts as a negative regulator of ERK phosphorylation, IL-2 promoter activity, and T cell proliferation.
  • Dok-4 activation of Rap1 is involved in ERK regulation.
  • The pleckstrin homology domain of Dok-4 is crucial for its localization and inhibitory function.

Conclusions:

  • Dok-4 is a novel negative regulator of T cell activation.
  • Dok-4 plays a significant role in T cell signaling pathways.
  • Understanding Dok-4's function provides insights into T cell regulation.

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