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Blood, 1 April 2007, Vol. 109, No. 7, pp. 2894-2902. Prepublished online as a Blood First Edition Paper on December 12, 2006; DOI 10.1182/blood-2006-07-038620. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-07-038620v1 109/7/2894    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Deane, J. A. Articles by Fruman, D. A. Search for Related Content PubMed PubMed Citation Articles by Deane, J. A. Articles by Fruman, D. A. Related Collections Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY T-cell function is partially maintained in the absence of class IA phosphoinositide 3-kinase signaling Jonathan A. Deane1, Michael G. Kharas1, Jean S. Oak1, Linda N. Stiles1, Ji Luo2,3, Travis I. Moore1, Hong Ji4, Christian Rommel4, Lewis C. Cantley2,3, Thomas E. Lane1,5, and David A. Fruman1,5 1 Department of Molecular Biology and Biochemistry, University of California, Irvine; 2 Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA; 3 Department of Systems Biology, Harvard Medical School, Boston, MA; 4 Serono Pharmaceutical Research Institute, Geneva, Switzerland; 5 Center for Immunology, University of California, Irvine The class IA subgroup of phosphoinositide 3-kinase (PI3K) is activated downstream of antigen receptors, costimulatory molecules, and cytokine receptors on lymphocytes. Targeted deletion of individual genes for class IA regulatory subunits severely impairs the development and function of B cells but not T cells. Here we analyze conditional mutant mice in which thymocytes and T cells lack the major class IA regulatory subunits p85, p55, p50, and p85ß. These cells exhibit nearly complete loss of PI3K signaling downstream of the T-cell receptor (TCR) and CD28. Nevertheless, T-cell development is largely unperturbed, and peripheral T cells show only partial impairments in proliferation and cytokine production in vitro. Both genetic and pharmacologic experiments suggest that class IA PI3K signaling plays a limited role in T-cell proliferation driven by TCR/CD28 clustering. In vivo, class IA–deficient T cells provide reduced help to B cells but show normal ability to mediate antiviral immunity. Together these findings provide definitive evidence that class IA PI3K regulatory subunits are essential for a subset of T-cell functions while challenging the notion that this signaling mechanism is a critical mediator of costimulatory signals downstream of CD28. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. J. de Souza, J. S. Oak, R. Jordanhazy, R. H. DeKruyff, D. A. Fruman, and L. P. Kane T Cell Ig and Mucin Domain-1-Mediated T Cell Activation Requires Recruitment and Activation of Phosphoinositide 3-Kinase J. Immunol., May 15, 2008; 180(10): 6518 - 6526. [Abstract] [Full Text] [PDF] S. J. Harris, R. V. Parry, J. Westwick, and S. G. Ward Phosphoinositide Lipid Phosphatases: Natural Regulators of Phosphoinositide 3-Kinase Signaling in T Lymphocytes J. Biol. Chem., February 1, 2008; 283(5): 2465 - 2469. [Abstract] [Full Text] [PDF] F. Garcon, D. T. Patton, J. L. Emery, E. Hirsch, R. Rottapel, T. Sasaki, and K. Okkenhaug CD28 provides T-cell costimulation and enhances PI3K activity at the immune synapse independently of its capacity to interact with the p85/p110 heterodimer Blood, February 1, 2008; 111(3): 1464 - 1471. [Abstract] [Full Text] [PDF] I. Alcazar, M. Marques, A. Kumar, E. Hirsch, M. Wymann, A. C. Carrera, and D. F. Barber Phosphoinositide 3 kinase {gamma} participates in T cell receptor induced T cell activation J. Exp. Med., November 26, 2007; 204(12): 2977 - 2987. [Abstract] [Full Text] [PDF] D. I. Albu, D. Feng, D. Bhattacharya, N. A. Jenkins, N. G. Copeland, P. Liu, and D. Avram BCL11B is required for positive selection and survival of double-positive thymocytes J. Exp. Med., November 26, 2007; 204(12): 3003 - 3015. [Abstract] [Full Text] [PDF] H.-R. Kim, K.-A Hwang, and I. Kang Dual Roles of IL-15 in Maintaining IL-7R{alpha}lowCCR7 Memory CD8+ T Cells in Humans via Recovering the Phosphatidylinositol 3-Kinase/AKT Pathway J. Immunol., November 15, 2007; 179(10): 6734 - 6740. [Abstract] [Full Text] [PDF] M. P. Matheu, J. A. Deane, I. Parker, D. A. Fruman, and M. D. Cahalan Class IA Phosphoinositide 3-Kinase Modulates Basal Lymphocyte Motility in the Lymph Node J. Immunol., August 15, 2007; 179(4): 2261 - 2269. [Abstract] [Full Text] [PDF]

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