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Title: Phosphoinositide 3–kinase γ participates in T cell receptor–induced T cell activation
Authors: Alcázar, Isabela, Marqués, Miriam, Kumar, Amit, Hirsch, Emilio, Wymann, Matthias P., Carrera, Ana C., Barber, Domingo F.
Issue Date: 6-Nov-2007
Publisher: Rockefeller University Press
Abstract: Class I phosphoinositide 3–kinases (PI3Ks) constitute a family of enzymes that generates 3-phosphorylated polyphosphoinositides at the cell membrane after stimulation of protein tyrosine (Tyr) kinase–associated receptors or G protein–coupled receptors (GPCRs). The class I PI3Ks are divided into two types: class I(A) p85/p110 heterodimers, which are activated by Tyr kinases, and the class I(B) p110γ isoform, which is activated by GPCR. Although the T cell receptor (TCR) is a protein Tyr kinase–associated receptor, p110γ deletion affects TCR-induced T cell stimulation. We examined whether the TCR activates p110γ, as well as the consequences of interfering with p110γ expression or function for T cell activation. We found that after TCR ligation, p110γ interacts with Gα(q/11), lymphocyte-specific Tyr kinase, and ζ-associated protein. TCR stimulation activates p110γ which affects 3-phosphorylated polyphosphoinositide levels at the immunological synapse. We show that TCR-stimulated p110γ controls RAS-related C3 botulinum substrate 1 activity, F-actin polarization, and the interaction between T cells and antigen-presenting cells, illustrating a crucial role for p110γ in TCR-induced T cell activation.
Description: 11 pages, 8 figures.-- PMID: 17998387 [PubMed].-- PMCID: PMC2118532.-- Printed version published Nov 26, 2007.
Supporting information attached: Information on Western blots, Immunoprecipitation assays, the Rac activation assay, the FACS-based conjugate formation assay, the Actin polymerization assay, and Stimulation with antibody-coated beads and immunofluorescence.-- Also available at:
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ISSN: 0022-1007
???metadata.dc.identifier.doi???: 10.1084/jem.20070366
Citation: Journal of Experimental Medicine 204(12): 2977-2987 (2007)
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