Tec kinase migrates to the T cell-APC interface independently of its pleckstrin homology domain.
Tec is the prototypical member of the Tec tyrosine kinases family, which plays an important role in T cell signaling. We show in this study that Tec translocates to the immunological synapse when a T cell contacts a dendritic cell. Surprisingly, the presence of the pleckstrin homology (PH) domain of Tec is not required for this accumulation, and despite a strong activation of 3'-phosphorylated phosphoinositide lipids synthesis during the synapse formation, the Tec PH domain is not redistributed to the T cell plasma membrane. In contrast, we demonstrate that an active Src homology 3 domain is absolutely required, underlining the essential role played by this part of the molecule in the recruitment and/or stabilization of Tec at the immunological synapse. Our results nevertheless suggest that the PH domain controls the kinase activity of the molecule in vivo. We finally demonstrate that the two domains are necessary to trigger transcriptional events following Ag presentation. These data support a model in which the plasma membrane recruitment of the PH-containing protein Tec is not dependent on the production of 3'-phosphorylated phosphoinositide lipids by the PI3K, but rather on an intact Src homology 3 domain.
Garçon
Fabien
F
Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 599, Université de la Méditerranée, Marseille, France.
Bismuth
Georges
G
Isnardon
Daniel
D
Olive
Daniel
D
Nunès
Jacques A
JA
D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D017385:Sequence Homology; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*
C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases