Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF) Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Alcázar, I. Articles by Barber, D. F. Search for Related Content PubMed PubMed Citation Articles by Alcázar, I. Articles by Barber, D. F. Social Bookmarking                      What's this?

Phosphoinositide 3–kinase participates in T cell receptor–induced T cell activation

¹ Department of Immunology and Oncology, Centro Nacional de Biotecnología (CNB)/Consejo Superior de Investigaciones Cientificas, Madrid 28049, Spain
² Department of Genetics Biology and Biochemistry, Center for Molecular Biotechnology, University of Torino, 10126 Turin, Italy
³ Department of Clinical and Biological Sciences, Institute of Biochemistry and Genetics, University of Basel, 4058 Basel, Switzerland

CORRESPONDENCE Domingo F. Barber: dfbarber{at}cnb.uam.es

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 p110 isoform, which is activated by GPCR. Although the T cell receptor (TCR) is a protein Tyr kinase–associated receptor, p110 deletion affects TCR-induced T cell stimulation. We examined whether the TCR activates p110, as well as the consequences of interfering with p110 expression or function for T cell activation. We found that after TCR ligation, p110 interacts with G_q/11, lymphocyte-specific Tyr kinase, and -associated protein. TCR stimulation activates p110, which affects 3-phosphorylated polyphosphoinositide levels at the immunological synapse. We show that TCR-stimulated p110 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 p110 in TCR-induced T cell activation.

Abbreviations used: CXCR, CXC chemokine receptor; GPCR, G protein–coupled receptor; IS, immunological synapse; ITAM, immunoreceptor Tyr-based activation motif; Lck, lymphocyte-specific Tyr kinase; MAPK, mitogen-activated protein kinase; PCC, pigeon cytochrome c; PH, pleckstrin homology; PI3K, phosphoinositide 3–kinase; PIP₂, phosphatidylinositol-3, 4-biphosphate; PIP₃, phosphatidylinositol-3,4,5-trisphosphate; PKB, protein kinase B; Rac1, RAS-related C3 botulinum substrate 1; SEE, staphylococcal enterotoxin E; SH2, Src homology 2; Tg, transgenic; TRIM, TCR-interacting molecule; Tyr, tyrosine; ZAP70, -associated protein.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Litherland, G. J., Dixon, C., Lakey, R. L., Robson, T., Jones, D., Young, D. A., Cawston, T. E., Rowan, A. D. (2008). Synergistic Collagenase Expression and Cartilage Collagenolysis Are Phosphatidylinositol 3-Kinase/Akt Signaling-dependent. J. Biol. Chem. 283: 14221-14229 [Abstract] [Full Text]  
• Alcazar, I., Marques, M., Kumar, A., Hirsch, E., Wymann, M., Carrera, A. C., Barber, D. F. (2007). Phosphoinositide 3 kinase {gamma} participates in T cell receptor induced T cell activation. J. Cell Biol. 179: i9-i9 [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS