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Blood, 15 November 2006, Vol. 108, No. 10, pp. 3428-3433. Prepublished online as a Blood First Edition Paper on August 3, 2006; DOI 10.1182/blood-2006-03-013821. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-03-013821v1 108/10/3428    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 Shipp, M. A. Search for Related Content PubMed PubMed Citation Articles by Chen, L. Articles by Shipp, M. A. Related Collections Signal Transduction Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Protein tyrosine phosphatase receptor–type O truncated (PTPROt) regulates SYK phosphorylation, proximal B-cell–receptor signaling, and cellular proliferation Linfeng Chen, Przemyslaw Juszczynski, Kunihiko Takeyama, Ricardo C. T. Aguiar, and Margaret A. Shipp From the Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA. The strength and duration of B-cell–receptor (BCR) signaling depends upon the balance between protein tyrosine kinase (PTK) activation and protein tyrosine phosphatase (PTP) inhibition. BCR-dependent activation of the SYK PTK initiates downstream signaling events and amplifies the original BCR signal. Although BCR-associated SYK phosphorylation is clearly regulated by PTPs, SYK has not been identified as a direct PTP substrate. Herein, we demonstrate that SYK is a major substrate of a tissue-specific and developmentally regulated PTP, PTP receptor–type O truncated (PTPROt). PTPROt is a member of the PTPRO family (also designated GLEPP, PTP-Ø, PTP-oc, and PTPu2), a group of highly conserved receptor-type PTPs that are thought to function as tumor suppressor genes. The overexpression of PTPROt inhibited BCR-triggered SYK tyrosyl phosphorylation, activation of the associated adaptor proteins SHC and BLNK, and downstream signaling events, including calcium mobilization and mitogen-activated protein kinase/extracellular signal–regulated kinase (MAPK/ERK) activation. PTPROt overexpression also inhibited lymphoma cell proliferation and induced apoptosis in the absence of BCR cross-linking, suggesting that the phosphatase modulates tonic BCR signaling. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Chen, S. Monti, P. Juszczynski, J. Daley, W. Chen, T. E. Witzig, T. M. Habermann, J. L. Kutok, and M. A. Shipp SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphoma Blood, February 15, 2008; 111(4): 2230 - 2237. [Abstract] [Full Text] [PDF] T. Motiwala, S. Majumder, H. Kutay, D. S. Smith, D. S. Neuberg, D. M. Lucas, J. C. Byrd, M. Grever, and S. T. Jacob Methylation and Silencing of Protein Tyrosine Phosphatase Receptor Type O in Chronic Lymphocytic Leukemia Clin. Cancer Res., June 1, 2007; 13(11): 3174 - 3181. [Abstract] [Full Text] [PDF] T. Wossning, S. Herzog, F. Kohler, S. Meixlsperger, Y. Kulathu, G. Mittler, A. Abe, U. Fuchs, A. Borkhardt, and H. Jumaa Deregulated Syk inhibits differentiation and induces growth factor-independent proliferation of pre-B cells J. Exp. Med., December 25, 2006; 203(13): 2829 - 2840. [Abstract] [Full Text] [PDF]

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