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Nature. 1995 Mar 30;374(6521):470-3.

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

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Division of Hematology/Oncology, Children's Hospital, Boston, Massachusetts 02115, USA.


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.

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