Cutting edge: Dok-1 and Dok-2 adaptor molecules are regulated by phosphatidylinositol 5-phosphate production in T cells Dok-1 and Dok-2 PH domains / PtdIns5P interactions

• Published in: The Journal of immunology (1950) Vol. 182; no. 7; pp. 3974 - 8
• Main Authors: Guittard, Geoffrey, Gérard, Audrey, Dupuis-Coronas, Sophie, Tronchère, Hélène, Mortier, Eva, Favre, Cédric, Olive, Daniel, Zimmermann, Pascale, Payrastre, Bernard, Nunès, Jacques
• Format: Journal Article
• Language: English
• Published: Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists 01.04.2009
• Subjects: Cancer; Cells-T Cells, Processes-Signal Transduction, Molecules-Protein Kinases/Phosphatases, Molecules-T Cell Receptors, Processes-Cell Activation; Immunology; Life Sciences; adapter molecules; phosphoinositides
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0804172

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.