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Blood, 1 July 2007, Vol. 110, No. 1, pp. 259-266. Prepublished online as a Blood First Edition Paper on March 15, 2007; DOI 10.1182/blood-2006-10-055194. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-10-055194v1 110/1/259    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 Ng, C.-H. Articles by Lam, K.-P. Search for Related Content PubMed PubMed Citation Articles by Ng, C.-H. Articles by Lam, K.-P. Related Collections Immunobiology Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Dok-3 plays a nonredundant role in negative regulation of B-cell activation Chee-Hoe Ng1, Shengli Xu1, and Kong-Peng Lam1,2 1 Laboratory of Molecular and Cellular Immunology, Biomedical Sciences Institutes, Agency for Science, Technology and Research (A*STAR) and 2 Singapore Immunology Network, Singapore p62dok and Dok-3 are members of the Dok family of adaptors found in B cells, with the former cloned as a substrate of the p210bcr/abl oncoprotein in Ph + chronic myelogenous leukemia. A role for p62dok in FcRIIB–mediated negative regulation of B-cell proliferation had been established previously. Here, we generated Dok-3–/– mice to assess the function of Dok-3 in B cells. Mice lacking Dok-3 have normal B-cell development but possess higher level of IgM antibodies in their sera. In comparison to wild-type mice, Dok-3–/– mice mounted significantly enhanced humoral immune responses to T cell–independent type I and II antigens. Dok-3–deficient B cells hyperproliferated, exhibited elevated level of calcium signaling as well as enhanced activation of NF-B, JNK, and p38MAPK in response to B-cell receptor (BCR) engagement. In the absence of Dok-3, the localization of the inhibitory phosphatase SHIP-1 to the plasma membrane is intact while its phosphorylation is compromised, suggesting that Dok-3 could function to facilitate or sustain the activation of SHIP-1. The phenotype and responses of Dok-3–/– mice and B cells could be differentiated from those of the Dok-1–/– counterparts. Hence, we propose that Dok-3 plays a distinct and nonredundant role in the negative regulation of BCR signaling. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Important port for SHIP-1 at Dok-3 Kerry S. Campbell Blood 2007 110: 3-4. [Full Text] [PDF] This article has been cited by other articles: V. Chew and K.-P. Lam Leupaxin Negatively Regulates B Cell Receptor Signaling J. Biol. Chem., September 14, 2007; 282(37): 27181 - 27191. [Abstract] [Full Text] [PDF]

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