Article (Scientific journals)
LYP inhibits T-cell activation when dissociated from CSK
Vang; Liu, Wallace H; Delacroix, Laurence et al.
2012In Nature Chemical Biology
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Abstract :
[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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Vang
Liu, Wallace H
Delacroix, Laurence ;  Université de Liège - ULiège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.
Wu, Shuangding
Vasile, Stefan
Dahl, Russell
Yang, Li
Musumeci, Lucia ;  Université de Liège - ULiège > 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  ;  Université de Liège - ULiège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.
Rickert, Robert C
Tautz, Lutz
More authors (8 more) Less
Language :
English
Title :
LYP inhibits T-cell activation when dissociated from CSK
Publication date :
2012
Journal title :
Nature Chemical Biology
ISSN :
1552-4450
eISSN :
1552-4469
Publisher :
Nature Publishing Group, New York, United States - New York
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 27 April 2012

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