Abstract
Src homology-2 domain-containing inositol polyphosphate 5'-phosphatase (SHIP) is a recently identified protein that has been implicated as an important signaling molecule. Although SHIP has been shown to participate in the FcgammaRIIB-mediated inhibitory signal, the functional role of SHIP in activation responses by immunoreceptor tyrosine-based activation motif-bearing receptors such as B cell receptor (BCR) remains unclear. Indeed, it has been proposed that SHIP serves as a linking molecule for the regulation of the extracellular signal-regulated kinase pathway in BCR signaling, because SHIP associates with Shc. We now report that SHIP-deficient DT40 B cells display enhanced Ca2+ mobilization in response to BCR ligation, whereas extracellular signal-regulated kinase activation is unaffected. This Ca2+ enhancement is due to a sustained intracellular Ca2+ increase or to long-lasting Ca2+ oscillations by loss of SHIP, as revealed by single-cell Ca2+ imaging analysis. These results demonstrate the importance of SHIP in B cell activation by the modulation of Ca2+ mobilization.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, CD / physiology
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism
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Calcium / metabolism
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Calcium Channels / metabolism
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Calcium Signaling / immunology*
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Cell Line
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Chickens
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Enzyme Activation / immunology
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Inositol 1,4,5-Trisphosphate / metabolism
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Inositol 1,4,5-Trisphosphate Receptors
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Membrane Proteins / metabolism
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Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
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Phosphoric Monoester Hydrolases / deficiency
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Phosphoric Monoester Hydrolases / genetics
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Phosphoric Monoester Hydrolases / physiology*
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Protein Binding / immunology
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Protein-Tyrosine Kinases / metabolism
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Receptors, Antigen, B-Cell / physiology*
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Receptors, Antigen, T-Cell / metabolism
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Receptors, Cytoplasmic and Nuclear / metabolism
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Receptors, IgG / physiology
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Transfection / immunology
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src Homology Domains / genetics
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src Homology Domains / immunology*
Substances
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Antigens, CD
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Calcium Channels
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Fc gamma receptor IIB
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ITPR1 protein, human
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Inositol 1,4,5-Trisphosphate Receptors
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Membrane Proteins
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Receptors, Antigen, B-Cell
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Receptors, Antigen, T-Cell
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Receptors, Cytoplasmic and Nuclear
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Receptors, IgG
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antigen T cell receptor, zeta chain
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Inositol 1,4,5-Trisphosphate
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Protein-Tyrosine Kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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Phosphoric Monoester Hydrolases
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INPPL1 protein, human
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Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
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Calcium