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Defective signalling through the T- and B-cell antigen receptors in lymphoid cells lacking the vav proto-oncogene

Nature volume 374, pages 470–473 (1995)Cite this article

Abstract

THE product of the vav proto-oncogene1, p95vav or Vav, is tyrosine phosphorylated upon stimulation of T and B cells by antigen2–4 and other5–8 receptors, and contains motifs associated with signal transduction1,9–11. To determine its role in vivo, we used t?at?-gene-targeted embryonic stem12 cells and RAG-2-/- blastocyst complementation13. 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-l (CD5+)14 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 ionophore15, whereas B cells responded normally to bacter-ial mitogen, lipopolysaccharide or the CD40 ligand16–18. Thus, we have established here a functional role for vav in the control of T-and B-cell development and activation.

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Authors and Affiliations

  1. Division of Hematology/Oncology, The Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts, 02115, USA

    Rong Zhang & Stuart H. Orkin

  2. Howard Hughes Medical Institute, Boston, Massachusetts, 02115, USA

    Frederick W. Alt, Laurie Davidson, Stuart H. Orkin & Wojciech Swat

  3. Dana Farber Cancer Insitute, Boston, Massachusetts, 02115, USA

    Rong Zhang & Stuart H. Orkin

  4. Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, 02115, USA

    Rong Zhang & Stuart H. Orkin

  5. Department of Genetics, Harvard Medical School, Boston, Massachusetts, 02115, USA

    Frederick W. Alt & Wojciech Swat

  6. Center for Blood Research, Boston, Massachusetts, 02115, USA

    Frederick W. Alt

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Zhang, R., Alt, F., Davidson, L. et al. Defective signalling through the T- and B-cell antigen receptors in lymphoid cells lacking the vav proto-oncogene. Nature 374, 470–473 (1995). https://doi.org/10.1038/374470a0

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