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Downstream of tyrosine kinase (Dok) proteins Dok-1 and Dok-2 are involved in T cell homeostasis maintenance. Dok protein tyrosine phosphorylation plays a key role in establishing negative feedback loops of T cell signaling. These structurally related adapter molecules contain a pleckstrin homology (PH) domain generally acting as a lipid/protein-interacting module. We show that the presence of this PH domain is necessary for the tyrosine phosphorylation of Dok proteins and their negative functions in T cells. We find that Dok-1/Dok-2 PH domains bind in vitro to the rare phosphoinositide species, phosphatidylinositol 5-phosphate (PtdIns5P). Dok tyrosine phosphorylation correlates with PtdIns5P production in T cells upon TCR triggering. Furthermore, we demonstrate that PtdIns5P increase regulates Dok tyrosine phosphorylation in vivo. Together, our data identify a novel lipid mediator in T cell signaling and suggest that PH-PtdIns5P interactions regulate T cell responses.

Original publication

DOI

10.4049/jimmunol.0804172

Type

Journal article

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Date

04/2009

Volume

182

Pages

3974 - 3978

Addresses

Institut National de la Santé et de la Recherche Médicale, Centre de Recherche en Cancérologie de Marseille, France.

Keywords

T-Lymphocytes, Hela Cells, Jurkat Cells, Humans, Phosphatidylinositol Phosphates, Adaptor Proteins, Signal Transducing, RNA-Binding Proteins, DNA-Binding Proteins, Phosphoproteins, Surface Plasmon Resonance, Lymphocyte Activation, Signal Transduction, Phosphorylation