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Blood, 15 February 2004, Vol. 103, No. 4, pp. 1425-1432. Prepublished online as a Blood First Edition Paper on October 16, 2003; DOI 10.1182/blood-2003-03-0716. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-03-0716v1 103/4/1425    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 Shrivastava, P. Articles by Yakura, H. Search for Related Content PubMed PubMed Citation Articles by Shrivastava, P. Articles by Yakura, H. Related Collections Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Dynamic regulation of Src-family kinases by CD45 in B cells Punya Shrivastava, Tatsuo Katagiri, Mami Ogimoto, Kazuya Mizuno, and Hidetaka Yakura From the Department of Immunology and Signal Transduction, Tokyo Metropolitan Institute for Neuroscience, Tokyo Metropolitan Organization for Medical Research, Fuchu, Tokyo, Japan; the Department of Biology, Toyama Medical and Pharmaceutical University, Toyama, Japan; and the Graduate School of Science, Tokyo Metropolitan University, Hachioji, Tokyo, Japan CD45 is a key protein tyrosine phosphatase regulating Src-family protein tyrosine kinases (Src-PTKs) in lymphocytes; precisely how it exerts its effect remains controversial, however. We previously demonstrated that CD45 negatively regulates Lyn in the WEHI-231 B-cell line. Here we show that negative regulation by CD45 is physiologically significant in B cells and that some CD45 is constitutively associated with glycolipid-enriched microdomains (GEMs), where it inhibits Src-PTKs by dephosphorylating both the negative and the positive regulatory sites. Upon B-cell receptor (BCR) ligation, however, CD45 dissociates from GEMs within 30 seconds, inducing phosphorylation of 2 regulatory sites and activation of Src-PTKs, but subsequently reassociates with the GEMs within 15 minutes. Disruption of GEMs with methyl--cyclodextrin results in abrogation of BCR-induced apoptosis in WEHI-231 cells, suggesting GEMs are critical to signals leading to the fate determination. We propose that the primary function of CD45 is inhibition of Src-PTKs and that the level of Src-PTK activation and the B-cell fate are determined in part by dynamic behavior of CD45 with respect to GEMs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J.-J. Hao, G. B. Carey, and X. Zhan Syk-mediated Tyrosine Phosphorylation Is Required for the Association of Hematopoietic Lineage Cell-specific Protein 1 with Lipid Rafts and B Cell Antigen Receptor Signalosome Complex J. Biol. Chem., August 6, 2004; 279(32): 33413 - 33420. [Abstract] [Full Text] [PDF]

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