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This Article Full Text Full Text (PDF) 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 Damen, J. E. Articles by Krystal, G. Search for Related Content PubMed PubMed Citation Articles by Damen, J. E. Articles by Krystal, G. Related Collections Signal Transduction Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 March 2001, Vol. 97, No. 5, pp. 1343-1351 IMMUNOBIOLOGY SHIP's C-terminus is essential for its hydrolysis of PIP3 and inhibition of mast cell degranulation Jacqueline E. Damen, Mark D. Ware, Janet Kalesnikoff, Michael R. Hughes, and Gerald Krystal From the Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada. The SH2-containing inositol-5'-phosphatase, SHIP, restrains bone marrow-derived mast cell (BMMC) degranulation, at least in part, by hydrolyzing phosphatidylinositol (PI)-3-kinase generated PI-3,4,5-P3 (PIP3) to PI-3,4-P2. To determine which domains within SHIP influence its ability to hydrolyze PIP3, bone marrow from SHIP/ mice was retrovirally infected with various SHIP constructs. Introduction of wild-type SHIP into SHIP/ BMMCs reverted the Steel factor (SF)-induced increases in PIP3, calcium entry, and degranulation to those observed in SHIP+/+ BMMCs. A 5'-phosphatase dead SHIP, however, could not revert the SHIP/ response, whereas a SHIP mutant in which the 2 NPXY motifs were converted to NPXFs (2NPXF) could partially revert the SHIP/ response. SF stimulation of BMMCs expressing the 2NPXF, which could not bind Shc, led to the same level of mitogen-activated protein kinase (MAPK) phosphorylation as that seen in BMMCs expressing the other constructs. Surprisingly, C-terminally truncated forms of SHIP, lacking different amounts of the proline rich C-terminus, could not revert the SHIP/ response at all. These results suggest that the C-terminus plays a critical role in enabling SHIP to hydrolyze PIP3 and inhibit BMMC degranulation. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. S. Ramshaw, M. A. Guthridge, F. C. Stomski, E. F. Barry, L. Ooms, C. A. Mitchell, C. G. Begley, and A. F. Lopez The Shc-binding site of the {beta}c subunit of the GM-CSF/IL-3/IL-5 receptors is a negative regulator of hematopoiesis Blood, November 15, 2007; 110(10): 3582 - 3590. [Abstract] [Full Text] [PDF] W.-H. Leung and S. Bolland The Inositol 5'-Phosphatase SHIP-2 Negatively Regulates IgE-Induced Mast Cell Degranulation and Cytokine Production J. Immunol., July 1, 2007; 179(1): 95 - 102. [Abstract] [Full Text] [PDF] J. Ai, A. Maturu, W. Johnson, Y. Wang, C. B. Marsh, and S. Tridandapani The inositol phosphatase SHIP-2 down-regulates Fc{gamma}R-mediated phagocytosis in murine macrophages independently of SHIP-1 Blood, January 15, 2006; 107(2): 813 - 820. [Abstract] [Full Text] [PDF] K. Gimborn, E. Lessmann, S. Kuppig, G. Krystal, and M. Huber SHIP Down-Regulates Fc{epsilon}R1-Induced Degranulation at Supraoptimal IgE or Antigen Levels J. Immunol., January 1, 2005; 174(1): 507 - 516. [Abstract] [Full Text] [PDF] M. G. Tomlinson, V. L. Heath, C. W. Turck, S. P. Watson, and A. Weiss SHIP Family Inositol Phosphatases Interact with and Negatively Regulate the Tec Tyrosine Kinase J. Biol. Chem., December 31, 2004; 279(53): 55089 - 55096. [Abstract] [Full Text] [PDF] Y. Wang, R. J. Keogh, M. G. 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