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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

Abstract : 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.
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https://www.hal.inserm.fr/inserm-00364224
Contributor : Jacques Nunès <>
Submitted on : Monday, March 23, 2009 - 11:30:50 AM
Last modification on : Tuesday, February 18, 2020 - 3:32:02 PM
Long-term archiving on: : Tuesday, June 8, 2010 - 9:08:38 PM

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Geoffrey Guittard, Audrey Gérard, Sophie Dupuis-Coronas, Hélène Tronchère, Eva Mortier, et al.. 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. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2009, 182 (7), pp.3974-8. ⟨10.4049/jimmunol.0804172⟩. ⟨inserm-00364224⟩

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