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Blood, 1 February 2007, Vol. 109, No. 3, pp. 1147-1155. Prepublished online as a Blood First Edition Paper on September 28, 2006; DOI 10.1182/blood-2006-02-001339. This Article Full Text Full Text (PDF) Supplemental Videos All Versions of this Article: blood-2006-02-001339v1 109/3/1147    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 Bach, T. L. Articles by Abrams, C. S. Search for Related Content PubMed PubMed Citation Articles by Bach, T. L. Articles by Abrams, C. S. Related Collections Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY PI3K regulates pleckstrin-2 in T-cell cytoskeletal reorganization Tami L. Bach1, Wesley T. Kerr1, Yanfeng Wang1, Eve Marie Bauman1, Purnima Kine1, Eileen L. Whiteman2, Renell S. Morgan3, Edward K. Williamson2, E. Michael Ostap4, Janis K. Burkhardt3, Gary A. Koretzky5, Morris J. Birnbaum2, and Charles S. Abrams1 1 Medicine, University of Pennsylvania School of Medicine, Philadelphia; 2 Howard Hughes Medical Institute, The Cox Institute, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia; 3 Department of Pathology, Children's Hospital of Philadelphia and the University of Pennsylvania; 4 Pennsylvania Muscle Institute and Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia; and 5 Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia Pleckstrin-2 is composed of 2 pleckstrin homology (PH) domains and a disheveled–Egl-10–pleckstrin (DEP) domain. A lipid-binding assay revealed that pleckstrin-2 binds with greatest affinity to D3 and D5 phosphoinositides. Pleckstrin-2 expressed in Jurkat T cells bound to the cellular membrane and enhanced actin-dependent spreading only after stimulation of the T-cell antigen receptor or the integrin 4ß1. A pleckstrin-2 variant containing point mutations in both PH domains failed to associate with the Jurkat membrane and had no effect on spreading under the same conditions. Although still membrane bound, a pleckstrin-2 variant containing point mutations in the DEP domain demonstrated a decreased ability to induce membrane ruffles and spread. Pleckstrin-2 also colocalized with actin at the immune synapse and integrin clusters via its PH domains. Although pleckstrin-2 can bind to purified D3 and D5 phosphoinositides, the intracellular membrane association of pleckstrin-2 and cell spreading are dependent on D3 phosphoinositides, because these effects were disrupted by pharmacologic inhibition of phosphatidylinositol 3-kinase (PI3K). Our results indicate that pleckstrin-2 uses its modular domains to bind to membrane-associated phosphatidylinositols generated by PI3K, whereby it coordinates with the actin cytoskeleton in lymphocyte spreading and immune synapse formation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Lian, Y. Wang, M. Flick, J. Choi, E. W. Scott, J. Degen, M. A. Lemmon, and C. S. Abrams Loss of pleckstrin defines a novel pathway for PKC-mediated exocytosis Blood, April 9, 2009; 113(15): 3577 - 3584. [Abstract] [Full Text] [PDF]

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