Reference : LYP inhibits T-cell activation when dissociated from CSK
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/118153
LYP inhibits T-cell activation when dissociated from CSK
English
Vang [ > > ]
Liu, Wallace H [ > > ]
Delacroix, Laurence mailto [Université de Liège - ULg > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén. >]
Wu, Shuangding [ > > ]
Vasile, Stefan [ > > ]
Dahl, Russell [ > > ]
Yang, Li [ > > ]
Musumeci, Lucia mailto [Université de Liège - ULg > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén. >]
Francis, Dana [ > > ]
Landskron, Johannes [ > > ]
Tasken, Tasken [ > > ]
Tremblay, Michel L [ > > ]
Lie, Benedicte A [ > > ]
Page, Rebecca [ > > ]
Mustelin, Tomas [ > > ]
Rahmouni, Souad mailto [Université de Liège - ULg > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén. >]
Rickert, Robert C [ > > ]
Tautz, Lutz [ > > ]
2012
Nature Chemical Biology
Nature Publishing Group
Yes (verified by ORBi)
International
1552-4450
1552-4469
New York
NY
[en] Lymphoid tyrosine phosphatase (LYP) and C-terminal Src kinase (CSK) are negative regulators of signaling mediated through the T-cell antigen receptor (TCR) and are thought to act in a cooperative manner when forming a complex. Here we studied the spatiotemporal dynamics of the LYP–CSK complex in T cells. We demonstrate that dissociation of this complex is necessary for recruitment of LYP to the plasma membrane, where it downmodulates TCR signaling. Development of a potent and selective chemical probe of LYP confirmed that LYP inhibits T-cell activation when removed from CSK. Our findings may explain the reduced TCR-mediated signaling associated with a single-nucleotide polymorphism that confers increased risk for certain autoimmune diseases, including type 1 diabetes and rheumatoid arthritis, and results in expression of a mutant LYP that is unable to bind CSK. Our compound also represents a starting point for the development of a LYP-based treatment of autoimmunity.
Researchers ; Professionals ; Students
http://hdl.handle.net/2268/118153
10.1038/nchembio.916

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