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Blood, 1 March 2008, Vol. 111, No. 5, pp. 2685-2692. Prepublished online as a Blood First Edition Paper on November 29, 2007; DOI 10.1182/blood-2006-12-062265. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-12-062265v1 111/5/2685    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 Chen, L. Articles by Kipps, T. J. Search for Related Content PubMed PubMed Citation Articles by Chen, L. Articles by Kipps, T. J. Related Collections Immunobiology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY ZAP-70 enhances IgM signaling independent of its kinase activity in chronic lymphocytic leukemia Liguang Chen1,2, Lang Huynh1,2, John Apgar3, Li Tang1,2, Laura Rassenti1,2, Arthur Weiss4, and Thomas J. Kipps1,2 1 Moores UCSD Cancer Center, University of California, San Diego; 2 Chronic Lymphocytic Leukemia (CLL) Research Consortium, San Diego, CA; 3 Department of Cell Signaling Research, BD PharMingen, San Diego, CA; and 4 Department of Medicine, Howard Hughes Medical Institute, University of California, San Francisco We transduced chronic lymphocytic leukemia (CLL) cells lacking ZAP-70 with vectors encoding ZAP-70 or various mutant forms of ZAP-70 and monitored the response of transduced CLL cells to treatment with F(ab)2 anti-IgM (anti-µ). CLL cells made to express ZAP-70, a kinase-defective ZAP-70 (ZAP-70-KA369), or a ZAP-70 unable to bind c-Cbl (ZAP-YF292) experienced greater intracellular calcium flux and had greater increases in the levels of phosphorylated p72Syk, B-cell linker protein (BLNK), and phospholipase C-, and greater activation of the Ig accessory molecule CD79b in response to treatment with anti-µ than did mock-transfected CLL cells lacking ZAP-70. Transfection of CLL cells with vectors encoding truncated forms of ZAP-70 revealed that the SH2 domain, but not the SH1 domain, was necessary to enhance intracellular calcium flux in response to treatment with anti-µ. We conclude that ZAP-70 most likely acts as an adapter protein that facilitates B-cell receptor (BCR) signaling in CLL cells independent of its tyrosine kinase activity or its ability to interact with c-Cbl. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Unveiling ZAP-70's plan B Amélie Montel-Hagen, Rita Vicente, and Naomi Taylor Blood 2008 111: 2501-2502. [Full Text] [PDF] This article has been cited by other articles: L. Z. Rassenti, S. Jain, M. J. Keating, W. G. Wierda, M. R. Grever, J. C. Byrd, N. E. Kay, J. R. Brown, J. G. Gribben, D. S. Neuberg, et al. Relative value of ZAP-70, CD38, and immunoglobulin mutation status in predicting aggressive disease in chronic lymphocytic leukemia Blood, September 1, 2008; 112(5): 1923 - 1930. [Abstract] [Full Text] [PDF] T. J. Kipps Chronic Lymphocytic Leukemia: Prognostic Markers and Revised Criteria for Treatment and Response Assessment ASCO Educational Book, January 1, 2008; 2008(1): 286 - 290. [Abstract] [Full Text] [PDF]

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