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ZAP-70 enhances IgM signaling independent of its kinase activity in chronic lymphocytic leukemia

Chen, Liguang, Huynh, Lang, Apgar, John, Tang, Li, Rassenti, Laura, Weiss, Arthur, Kipps, Thomas J.·2008·Blood
DOI 10.1182/blood-2006-12-062265
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Abstract

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-γ, 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.

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Metadata

Authors
Chen, L., Huynh, L., Apgar, J., Tang, L., Rassenti, L., Weiss, A., & Kipps, T. J.
Affiliations
  • Moores UCSD Cancer Center, University of California, San Diego;
  • Department of Cell Signaling Research, BD PharMingen, San Diego, CA; and
  • Department of Medicine, Howard Hughes Medical Institute, University of California, San Francisco
Venue
Blood
Publisher
American Society of Hematology
Published
2008-03-01
Volume
111
Issue
5
Pages
2685-2692
ISSN
  • 0006-4971
  • 1528-0020
DOI
10.1182/blood-2006-12-062265
Cited by
131
References
0
Language
en

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CoChat. (2026). Citation check: ZAP-70 enhances IgM signaling independent of its kinase activity in chronic lymphocytic leukemia. https://app.cochat.ai/papers/10.1182/blood-2006-12-062265
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Chen, L., Huynh, L., Apgar, J., Tang, L., Rassenti, L., Weiss, A., & Kipps, T. J. (2008). ZAP-70 enhances IgM signaling independent of its kinase activity in chronic lymphocytic leukemia. Blood. https://doi.org/10.1182/blood-2006-12-062265

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