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    J Exp Med. 1998 Oct 5;188(7):1333-42.

    The inositol polyphosphate 5-phosphatase ship is a crucial negative regulator of B cell antigen receptor signaling.

    Liu Q, Oliveira-Dos-Santos AJ, Mariathasan S, Bouchard D, Jones J, Sarao R, Kozieradzki I, Ohashi PS, Penninger JM, Dumont DJ.

    Amgen Institute, Toronto, Ontario, Canada M5G 2C1. qliu@amgen.com

    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 Fcgamma receptor IIB (FcgammaRIIB), a low affinity receptor for the Fc portion of immunoglobulin (Ig)G, and is rapidly tyrosine phosphorylated upon B cell antigen receptor (BCR)-FcgammaRIIB 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-FcgammaRIIB coligation. These results demonstrate that Ship plays an essential role in FcgammaRIIB-mediated inhibition of BCR signaling, and that Ship is a crucial negative regulator of Ca2+ flux and MAPK activation.

    PMID: 9763612 [PubMed - indexed for MEDLINE]

    PMCID: 2212495

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