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Blood, 15 January 2009, Vol. 113, No. 3, pp. 594-603. Prepublished online as a Blood First Edition Paper on October 7, 2008; DOI 10.1182/blood-2008-04-150987. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-04-150987v1 113/3/594    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Parikh, K. Articles by Visser, L. Search for Related Content PubMed PubMed Citation Articles by Parikh, K. Articles by Visser, L. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Extracellular ligation-dependent CD45RB enzymatic activity negatively regulates lipid raft signal transduction Kaushal Parikh1, Sibrand Poppema2, Maikel P. Peppelenbosch1, and Lydia Visser2 Departments of1 Cell Biology and 2 Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands CD45 is the most prominent membrane protein on lymphocytes. The function and regulation of this protein tyrosine phosphatase remain largely obscure, mainly because of the lack of a known ligand, and it still remains unknown whether such tyrosine phosphatases are subject to extracellular control at all. We report that an anti-CD45RB antibody (Ab) that prevents rejection and induces tolerance activates CD45RB tyrosine phosphatase enzymatic activity in T lymphocytes, allowing us to directly monitor the effects of increased CD45RB activity on signal transduction. Using both kinase substrate peptide arrays as well as conventional biochemistry, we also provide evidence of the various kinases involved in bringing about the inhibitory effect of this Ab on CD3-induced T-cell receptor signaling. Furthermore, we report that activated CD45RB translocates to lipid rafts and interferes with lipid raft localization and activation state of CD45 substrate Lck. Thus, these findings indeed prove that CD45 is subject to extracellular control and also define a novel mechanism by which receptor tyrosine phosphatases control lymphocyte biology and provide further insight into the intracellular signaling pathways effected by anti-CD45RB monoclonal Ab treatment. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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