Dynamic interaction between lymphoid tyrosine phosphatase and C-terminal Src kinase controls T cell activation -- Tautz et al. 26 (1): 766.11 -- The FASEB Journal.pdf
[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 show that dissociation of the LYP/CSK complex is necessary for recruitment of LYP to lipid rafts, where it down-modulates TCR-mediated signaling. Our findings may also explain the reduced TCR signaling associated with a single nucleotide polymorphism, which confers increased risk for autoimmunity and results in the expression of a LYP allele that can no longer bind CSK. Development of a potent and selective chemical probe of LYP allowed us to confirm that the observed down-modulation of TCR-induced signaling was due to the LYP catalytic activity. 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 :
Tautz, Lutz
Vang, Torkel
Liu, Wallace
Delacroix, Laurence ; Université de Liège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Wu, Shuangding
Vasile, Stefan
Dahl, Russel
Yang, Li
MUSUMECI, Lucia ; Centre Hospitalier Universitaire de Liège - CHU > Centre d'oncologie
Francis, Dana
Landskron, Johannes
Tasken, Kjetil
Tremblay, Michel
Lie, Benedicte
Page, Rebecca
Mustelin, Tomas
Rahmouni, Souad ; Université de Liège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.