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Blood, 1 December 2008, Vol. 112, No. 12, pp. 4617-4627. Prepublished online as a Blood First Edition Paper on September 16, 2008; DOI 10.1182/blood-2007-11-121111. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-11-121111v1 112/12/4617    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 Letschka, T. Articles by Baier, G. Search for Related Content PubMed PubMed Citation Articles by Letschka, T. Articles by Baier, G. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY PKC- selectively controls the adhesion-stimulating molecule Rap1 Thomas Letschka1, Veronika Kollmann1, Christa Pfeifhofer-Obermair1, Christina Lutz-Nicoladoni1, Gerald J. Obermair2, Friedrich Fresser1, Michael Leitges3, Natascha Hermann-Kleiter1, Sandra Kaminski1, and Gottfried Baier1 1 Department for Medical Genetics, Molecular and Clinical Pharmacology and 2 Department for Physiology and Medical Physics, Innsbruck Medical University, Innsbruck, Austria; and 3 Biotechnology Centre of Oslo, University of Oslo, Oslo, Norway The antigen-specific interaction of a T cell with an antigen-presenting cell (APC) results in the formation of an immunologic synapse (IS) between the membranes of the 2 cells. β2 integrins on the T cell, namely, leukocyte function-associated antigen 1 (LFA-1) and its counter ligand, namely, immunoglobulin-like cell adhesion molecule 1 (ICAM-1) on the APC, critically stabilize this intercellular interaction. The small GTPase Rap1 controls T-cell adhesion through modulating the affinity and/or spatial organization of LFA-1; however, the upstream regulatory components triggered by the T-cell receptor (TCR) have not been resolved. In the present study, we identified a previously unknown function of a protein kinase C- (PKC-)/RapGEF2 complex in LFA-1 avidity regulation in T lymphocytes. After T-cell activation, the direct phosphorylation of RapGEF2 at Ser960 by PKC- regulates Rap1 activation as well as LFA-1 adhesiveness to ICAM-1. In OT-II TCR-transgenic CD4+ T cells, clustering of LFA-1 after antigen activation was impaired in the absence of PKC-. These data define that, among other pathways acting on LFA-1 regulation, PKC- and its effector RapGEF2 are critical factors in TCR signaling to Rap1. Taken together, PKC- sets the threshold for T-cell activation by positively regulating both the cytokine responses and the adhesive capacities of T lymphocytes. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Horn, X. Wang, P. Reichardt, T. E. Stradal, N. Warnecke, L. Simeoni, M. Gunzer, D. Yablonski, B. Schraven, and S. Kliche Src Homology 2-Domain Containing Leukocyte-Specific Phosphoprotein of 76 kDa Is Mandatory for TCR-Mediated Inside-Out Signaling, but Dispensable for CXCR4-Mediated LFA-1 Activation, Adhesion, and Migration of T Cells J. Immunol., November 1, 2009; 183(9): 5756 - 5767. [Abstract] [Full Text] [PDF] J.-P. Evenou, J. Wagner, G. Zenke, V. Brinkmann, K. Wagner, J. Kovarik, K. A. Welzenbach, G. Weitz-Schmidt, C. Guntermann, H. Towbin, et al. The Potent Protein Kinase C-Selective Inhibitor AEB071 (Sotrastaurin) Represents a New Class of Immunosuppressive Agents Affecting Early T-Cell Activation J. Pharmacol. Exp. Ther., September 1, 2009; 330(3): 792 - 801. [Abstract] [Full Text] [PDF] T. Gruber, N. Hermann-Kleiter, R. Hinterleitner, F. Fresser, R. Schneider, G. Gastl, J. M. Penninger, and G. Baier PKC-{theta} Modulates the Strength of T Cell Responses by Targeting Cbl-b for Ubiquitination and Degradation Sci. Signal., June 23, 2009; 2(76): ra30 - ra30. [Abstract] [Full Text] [PDF] M. Huse The T-cell-receptor signaling network J. Cell Sci., May 1, 2009; 122(9): 1269 - 1273. [Full Text] [PDF]

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