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Blood, 1 March 2007, Vol. 109, No. 5, pp. 2032-2039. Prepublished online as a Blood First Edition Paper on October 12, 2006; DOI 10.1182/blood-2006-03-011759. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-03-011759v1 109/5/2032    most recent Alert me when this article is cited Alert me if a correction is posted 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 Gobessi, S. Articles by Efremov, D. G Search for Related Content PubMed PubMed Citation Articles by Gobessi, S. Articles by Efremov, D. G Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 21, 2006 Accepted October 10, 2006 ZAP-70 enhances B-cell receptor signaling in spite of absent or inefficient tyrosine kinase activation in chronic lymphocytic leukemia and lymphoma B-cells Stefania Gobessi, Luca Laurenti, Pablo G Longo, Simona Sica, Giuseppe Leone, and Dimitar G Efremov* ICGEB Outstation - Monterotondo, CNR Campus "Adriano Buzzati-Traverso", Rome, Italy Hematology Institute, Universita Cattolica del Sacro Cuore, Rome, Italy * Corresponding author; email: efremov{at}icgeb.org. Expression of ZAP-70 is an important negative prognostic factor in chronic lymphocytic leukemia (CLL). This protein tyrosine kinase is a key mediator of T-cell receptor (TCR) signaling and is structurally homologous to Syk, which plays an analogous role in B-cell receptor (BCR) signaling. Recent studies indicate that ZAP-70 may participate in BCR signaling as well, but the mechanism of action is not completely understood. We have now compared antigen-receptor induced activation of ZAP-70 in B-cells and T-cells by analyzing phosphorylation of critical regulatory tyrosine residues. We show that BCR-mediated activation of ZAP-70 is very inefficient in CLL and lymphoma B-cells and is negligible when compared to activation of Syk. Despite the inefficient catalytic activation, the ability of ZAP-70 to recruit downstream signaling molecules in response to antigen-receptor stimulation appeared relatively preserved. Moreover, ectopic expression of ZAP-70 was found to enhance and prolong activation of several key mediators of BCR signaling, such as the Syk, ERK and Akt kinases, and to decrease the rate of ligand-mediated BCR internalization. We conclude that the role of ZAP-70 in BCR signaling is quite distinct from its role in TCR signaling and is likely mediated by inhibition of events that terminate the signaling response. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Herling, K. A. Patel, N. Weit, N. Lilienthal, M. Hallek, M. J. Keating, and D. Jones High TCL1 levels are a marker of B-cell receptor pathway responsiveness and adverse outcome in chronic lymphocytic leukemia Blood, November 19, 2009; 114(21): 4675 - 4686. [Abstract] [Full Text] [PDF] R. M. Young, I. R. Hardy, R. L. Clarke, N. Lundy, P. Pine, B. C. Turner, T. A. Potter, and Y. Refaeli Mouse models of non-Hodgkin lymphoma reveal Syk as an important therapeutic target Blood, March 12, 2009; 113(11): 2508 - 2516. [Abstract] [Full Text] [PDF] J. BOELENS, S. LUST, B. VANHOECKE, and F. OFFNER Chronic Lymphocytic Leukaemia Anticancer Res, February 1, 2009; 29(2): 605 - 615. 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