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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 30, 2006 Accepted July 10, 2006 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* Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA * Corresponding author; email: margaret_shipp{at}dfci.harvard.edu. 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, PTPROt. PTPROt is a member of the PTPRO family (also designated GLEPP, PTP-, 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 tryosyl phosphorylation, activation of the associated adaptor proteins SHC and BLNK, and downstream signaling events including calcium mobilization and MAPK/ERK activation. PTPROt overexpression also inhibited lymphoma cell proliferation and induced apoptosis in the absence of BCR crosslinking, 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: D. S. Charba, R. C. Wiggins, M. Goyal, B. L. Wharram, J. E. Wiggins, E. T. McCarthy, R. Sharma, M. Sharma, and V. J. Savin Antibodies to protein tyrosine phosphatase receptor type O (PTPro) increase glomerular albumin permeability (Palb) Am J Physiol Renal Physiol, July 1, 2009; 297(1): F138 - F144. [Abstract] [Full Text] [PDF] R. P. Gobert, M. van den Eijnden, C. Szyndralewiez, C. Jorand-Lebrun, D. Swinnen, L. Chen, C. Gillieron, F. Pixley, P. Juillard, P. Gerber, et al. GLEPP1/Protein-tyrosine Phosphatase {phi} Inhibitors Block Chemotaxis in Vitro and in Vivo and Improve Murine Ulcerative Colitis J. Biol. Chem., April 24, 2009; 284(17): 11385 - 11395. [Abstract] [Full Text] [PDF] T. Motiwala, S. Majumder, K. Ghoshal, H. Kutay, J. Datta, S. Roy, D. M. Lucas, and S. T. Jacob PTPROt Inactivates the Oncogenic Fusion Protein BCR/ABL and Suppresses Transformation of K562 Cells J. Biol. Chem., January 2, 2009; 284(1): 455 - 464. [Abstract] [Full Text] [PDF] 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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