title: Beta-catenin inhibits T cell activation by selective interference with linker for activation of T cells-phospholipase C-γ1 phosphorylation.
abstract: Despite the defined function of the β-catenin pathway in thymocytes, its functional role in peripheral T cells is poorly understood. We report that in a mouse model, β-catenin protein is constitutively degraded in peripheral T cells. Introduction of stabilized β-catenin into primary T cells inhibited proliferation and cytokine secretion after TCR stimulation and blunted effector cell differentiation. Functional and biochemical studies revealed that β-catenin selectively inhibited linker for activation of T cells phosphorylation on tyrosine 136, which was associated with defective phospholipase C-γ1 phosphorylation and calcium signaling but normal ERK activation. Our findings indicate that β-catenin negatively regulates T cell activation by a previously undescribed mechanism and suggest that conditions under which β-catenin might be inducibly stabilized in vivo would be inhibitory for T cell-based immunity.
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Driessens
authors.forename: Yan
authors.initials: Y
authors.lastname: Zheng
authors.forename: Frederick
authors.initials: F
authors.lastname: Locke
authors.forename: Judy L
authors.initials: JL
authors.lastname: Cannon
authors.forename: Fotini
authors.initials: F
authors.lastname: Gounari
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Gajewski
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D051966:Phospholipase C gamma / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010750:Phosphoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010766:Phosphorylation / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011991:Receptors, Virus / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D014158:Transcription, Genetic / Q000276:immunology; D051176:beta Catenin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C568772:CLMP protein, mouse; C495267:CTNNB1 protein, mouse; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D016207:Cytokines; D007166:Immunosuppressive Agents; C491734:Lat protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D011991:Receptors, Virus; D051176:beta Catenin; D051966:Phospholipase C gamma