Zhang R, Alt F W, Davidson L, Orkin S H, Swat W
Division of Hematology/Oncology, Children's Hospital, Boston, Massachusetts 02115, USA.
Nature. 1995 Mar 30;374(6521):470-3. doi: 10.1038/374470a0.
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.
原癌基因vav的产物p95vav或Vav，在抗原和其他受体刺激T细胞和B细胞后会发生酪氨酸磷酸化，并且含有与信号转导相关的基序。为了确定其在体内的作用，我们使用了vav基因靶向的胚胎干细胞和RAG - 2 - / - 囊胚互补技术。vav(-/-)-RAG-2-/-嵌合体表现出胸腺萎缩，外周T细胞数量减少。虽然B细胞总数正常，但腹膜B-1（CD5+）细胞亚群缺失。当通过抗原受体刺激时，vav-/- T细胞和B细胞反应低下，但vav-/- T细胞在接触佛波酯和钙离子载体时会增殖，而B细胞对细菌有丝分裂原、脂多糖或CD40配体反应正常。因此，我们在此确定了vav在T细胞和B细胞发育及激活控制中的功能作用。
