The Journal of Immunology · 2009 · 58 citations · 21 references
Life SciencesImmunologyMolecular BiologyCell SignalingMolecular Cell BiologySignal TransductionAdaptor Protein ComplexesLipid SignalingPhosphoinositide SignalingProtein Kinase CascadesT Cell ActivationT Cell BiologyAdaptor Protein Function In T Cell SignalingImmune Cell HomeostasisNegative FeedbackPh DomainsPhosphatidylinositol 3, 4, 5-Trisphosphate SignalingPleckstrin Homology DomainsProtein Tyrosine PhosphorylationTyrosine Phosphorylation Signaling
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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A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate
Lucia E. Rameh, Kimberley F. Tolias, Brian Duckworth et al. · Nature · 1997 · 456 citations