Abstract
The product of the vav proto-oncogene, p95vav or Vav, is tyrosine phosphorylated upon stimulation of T and B cells by antigen and other receptors, and contains motifs associated with signal transduction. To determine its role in vivo, we used vav-gene-targeted embryonic stem cells and RAG-2-/- blastocyst complementation. The vav(-/-)-RAG-2-/- chimaeras displayed thymic atrophy with reduced numbers of peripheral T cells. Whereas the total number of B cells was normal, the subset of peritoneal B-1 (CD5+) cells was missing. The vav-/- T and B cells were hyporeactive when stimulated through antigen receptors, but vav-/- T cells proliferated on exposure to phorbol ester and calcium ionophore, whereas B cells responded normally to bacterial mitogen, lipopolysaccharide or the CD40 ligand. Thus, we have established here a functional role for vav in the control of T- and B-cell development and activation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / biosynthesis
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Antigens, Differentiation, T-Lymphocyte / biosynthesis
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B-Lymphocytes / cytology*
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B-Lymphocytes / metabolism
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Cell Cycle Proteins*
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Cell Differentiation / physiology
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Cell Line
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Chimera
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DNA-Binding Proteins*
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Lectins, C-Type
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Mice
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Proteins / genetics
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Proteins / metabolism
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Proto-Oncogene Proteins / physiology*
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Proto-Oncogene Proteins c-vav
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Receptors, Antigen, B-Cell / metabolism*
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Receptors, Antigen, T-Cell / metabolism*
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Signal Transduction*
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T-Lymphocytes / cytology*
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T-Lymphocytes / metabolism
Substances
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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CD69 antigen
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Cell Cycle Proteins
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DNA-Binding Proteins
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Lectins, C-Type
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Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-vav
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Rag2 protein, mouse
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Receptors, Antigen, B-Cell
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Receptors, Antigen, T-Cell
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V(D)J recombination activating protein 2
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Vav1 protein, mouse