Ship is an Src homology 2 domain containing inositol polyphosphate 5-phosphatase which has been implicated as an important signaling molecule in hematopoietic cells. In B cells, Ship becomes associated with Fcγ receptor IIB (FcγRIIB), a low affinity receptor for the Fc portion of immunoglobulin (Ig)G, and is rapidly tyrosine phosphorylated upon B cell antigen receptor (BCR)–FcγRIIB coligation. The function of Ship in lymphocytes was investigated in Ship−/− recombination-activating gene (Rag)−/− chimeric mice generated from gene-targeted Ship−/− embryonic stem cells. Ship−/−Rag−/− chimeras showed reduced numbers of B cells and an overall increase in basal serum Ig. Ship−/− splenic B cells displayed prolonged Ca2+ influx, increased proliferation in vitro, and enhanced mitogen-activated protein kinase (MAPK) activation in response to BCR–FcγRIIB coligation. These results demonstrate that Ship plays an essential role in FcγRIIB-mediated inhibition of BCR signaling, and that Ship is a crucial negative regulator of Ca2+ flux and MAPK activation.
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5 October 1998
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October 05 1998
The Inositol Polyphosphate 5-Phosphatase Ship Is a Crucial Negative Regulator of B Cell Antigen Receptor Signaling
Qiurong Liu,
Qiurong Liu
From the *Amgen Institute, Toronto, Ontario, Canada M5G 2C1; the ‡Department of Medical Biophysics and the §Department of Immunology, University of Toronto, Ontario, Canada M5G 2M9; and the ‖Ontario Cancer Institute, Toronto, Ontario, Canada M5G 2M9
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Antonio J. Oliveira-Dos-Santos,
Antonio J. Oliveira-Dos-Santos
From the *Amgen Institute, Toronto, Ontario, Canada M5G 2C1; the ‡Department of Medical Biophysics and the §Department of Immunology, University of Toronto, Ontario, Canada M5G 2M9; and the ‖Ontario Cancer Institute, Toronto, Ontario, Canada M5G 2M9
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Sanjeev Mariathasan,
Sanjeev Mariathasan
From the *Amgen Institute, Toronto, Ontario, Canada M5G 2C1; the ‡Department of Medical Biophysics and the §Department of Immunology, University of Toronto, Ontario, Canada M5G 2M9; and the ‖Ontario Cancer Institute, Toronto, Ontario, Canada M5G 2M9
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Denis Bouchard,
Denis Bouchard
From the *Amgen Institute, Toronto, Ontario, Canada M5G 2C1; the ‡Department of Medical Biophysics and the §Department of Immunology, University of Toronto, Ontario, Canada M5G 2M9; and the ‖Ontario Cancer Institute, Toronto, Ontario, Canada M5G 2M9
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Jamie Jones,
Jamie Jones
From the *Amgen Institute, Toronto, Ontario, Canada M5G 2C1; the ‡Department of Medical Biophysics and the §Department of Immunology, University of Toronto, Ontario, Canada M5G 2M9; and the ‖Ontario Cancer Institute, Toronto, Ontario, Canada M5G 2M9
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Renu Sarao,
Renu Sarao
From the *Amgen Institute, Toronto, Ontario, Canada M5G 2C1; the ‡Department of Medical Biophysics and the §Department of Immunology, University of Toronto, Ontario, Canada M5G 2M9; and the ‖Ontario Cancer Institute, Toronto, Ontario, Canada M5G 2M9
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Ivona Kozieradzki,
Ivona Kozieradzki
From the *Amgen Institute, Toronto, Ontario, Canada M5G 2C1; the ‡Department of Medical Biophysics and the §Department of Immunology, University of Toronto, Ontario, Canada M5G 2M9; and the ‖Ontario Cancer Institute, Toronto, Ontario, Canada M5G 2M9
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Pamela S. Ohashi,
Pamela S. Ohashi
From the *Amgen Institute, Toronto, Ontario, Canada M5G 2C1; the ‡Department of Medical Biophysics and the §Department of Immunology, University of Toronto, Ontario, Canada M5G 2M9; and the ‖Ontario Cancer Institute, Toronto, Ontario, Canada M5G 2M9
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Josef M. Penninger,
Josef M. Penninger
From the *Amgen Institute, Toronto, Ontario, Canada M5G 2C1; the ‡Department of Medical Biophysics and the §Department of Immunology, University of Toronto, Ontario, Canada M5G 2M9; and the ‖Ontario Cancer Institute, Toronto, Ontario, Canada M5G 2M9
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Daniel J. Dumont
Daniel J. Dumont
From the *Amgen Institute, Toronto, Ontario, Canada M5G 2C1; the ‡Department of Medical Biophysics and the §Department of Immunology, University of Toronto, Ontario, Canada M5G 2M9; and the ‖Ontario Cancer Institute, Toronto, Ontario, Canada M5G 2M9
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Qiurong Liu,
Antonio J. Oliveira-Dos-Santos,
Sanjeev Mariathasan,
Denis Bouchard,
Jamie Jones,
Renu Sarao,
Ivona Kozieradzki,
Pamela S. Ohashi,
Josef M. Penninger,
Daniel J. Dumont
From the *Amgen Institute, Toronto, Ontario, Canada M5G 2C1; the ‡Department of Medical Biophysics and the §Department of Immunology, University of Toronto, Ontario, Canada M5G 2M9; and the ‖Ontario Cancer Institute, Toronto, Ontario, Canada M5G 2M9
Address correspondence to Qiurong Liu, Amgen Institute, 620 University Avenue, Suite 706, Toronto, Canada, M5G 2C1. Phone: 416-204-2264; Fax: 416-204-2277; E-mail: [email protected]
Received:
April 20 1998
Revision Received:
June 23 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1998
J Exp Med (1998) 188 (7): 1333–1342.
Article history
Received:
April 20 1998
Revision Received:
June 23 1998
Citation
Qiurong Liu, Antonio J. Oliveira-Dos-Santos, Sanjeev Mariathasan, Denis Bouchard, Jamie Jones, Renu Sarao, Ivona Kozieradzki, Pamela S. Ohashi, Josef M. Penninger, Daniel J. Dumont; The Inositol Polyphosphate 5-Phosphatase Ship Is a Crucial Negative Regulator of B Cell Antigen Receptor Signaling . J Exp Med 5 October 1998; 188 (7): 1333–1342. doi: https://doi.org/10.1084/jem.188.7.1333
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