Abstract
Many receptors activate phospholipase Cgamma1 or -gamma2. To assess the role of PLCgamma2, we derived enzyme-deficient mice. The mice are viable but have decreased mature B cells, a block in pro-B cell differentiation, and B1 B cell deficiency. IgM receptor-induced Ca2+ flux and proliferation to B cell mitogens are absent. IgM, IgG2a, and IgG3 levels are reduced, and T cell-independent antibody production is absent. The similarity to Btk- or Blnk-deficient mice demonstrates that PLCgamma2 is downstream in Btk/Blnk signaling. FcRgamma signaling is also defective, resulting in a loss of collagen-induced platelet aggregation, mast cell FcepsilonR function, and NK cell FcgammaRIII and 2B4 function. The results define a signal transduction pathway broadly utilized by immunoglobulin superfamily receptors.
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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Adaptor Proteins, Signal Transducing
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Agammaglobulinaemia Tyrosine Kinase
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Animals
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B-Lymphocytes / metabolism
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B-Lymphocytes / physiology*
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Blood Platelets / physiology
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Carrier Proteins / metabolism
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Hematopoiesis / physiology
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Isoenzymes / genetics
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Isoenzymes / physiology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Phospholipase C gamma
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Phosphoproteins / metabolism
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Protein-Tyrosine Kinases / metabolism
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Receptors, Antigen, B-Cell / metabolism
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Receptors, IgG / metabolism
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Receptors, IgG / physiology*
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Type C Phospholipases / genetics
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Type C Phospholipases / physiology*
Substances
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Adaptor Proteins, Signal Transducing
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B cell linker protein
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Carrier Proteins
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Isoenzymes
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Phosphoproteins
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Receptors, Antigen, B-Cell
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Receptors, IgG
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Protein-Tyrosine Kinases
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Agammaglobulinaemia Tyrosine Kinase
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Type C Phospholipases
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Phospholipase C gamma