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
- Resource Type
- Authors
- Daniel Olive; Bernard Payrastre; Sophie Dupuis-Coronas; Hélène Tronchère; Jacques A. Nunès; Eva Mortier; Geoffrey Guittard; Audrey Gérard; Cédric Favre; Pascale Zimmermann
- Source
- Journal of Immunology
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⟩
- Subject
- T-Lymphocytes
Immunology
[SDV.CAN]Life Sciences [q-bio]/Cancer
Protein tyrosine phosphatase
Lymphocyte Activation
SH2 domain
Receptor tyrosine kinase
Jurkat Cells
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Phosphatidylinositol Phosphates
Humans
Immunology and Allergy
Phosphatidylinositol
Phosphorylation
Phosphatidylinositol 5-phosphate
Adaptor Proteins, Signal Transducing
030304 developmental biology
0303 health sciences
MESH: Cells-T Cells, Processes-Signal Transduction, Molecules-Protein Kinases/Phosphatases, Molecules-T Cell Receptors, Processes-Cell Activation
biology
adapter molecules
RNA-Binding Proteins
Tyrosine phosphorylation
phosphoinositides
Surface Plasmon Resonance
Phosphoproteins
Cell biology
DNA-Binding Proteins
Pleckstrin homology domain
chemistry
Biochemistry
biology.protein
[SDV.IMM]Life Sciences [q-bio]/Immunology
030217 neurology & neurosurgery
HeLa Cells
Signal Transduction
- Language
- English
- ISSN
- 0022-1767
1550-6606
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.