Defective signalling through the T- and B-cell antigen receptors in lymphoid cells lacking the vav proto-oncogene
Defective signalling through the T- and B-cell antigen receptors in lymphoid cells lacking the vav proto-oncogene
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缺乏 vav 原癌基因的淋巴细胞中 T 细胞和 B 细胞抗原受体的信号传导缺陷
作者：
Rong Zhang;F. Alt;L. Davidson;S. Orkin;W. Swat
vav原癌基因1的产物p95vav或vav，在抗原2 - 4和其他5 - 8受体刺激T细胞和B细胞时酪氨酸磷酸化，并包含与信号转导相关的基序1,9 - 11。为了确定其在体内的作用，我们使用了t？-基因靶向胚胎干细胞与RAG-2-/-囊胚互补vav-/——rag2 -/-嵌合体表现出胸腺萎缩，外周血T细胞数量减少。B细胞总数正常，腹膜B- 1 (CD5+)14细胞亚群缺失。当抗原受体刺激vav-/- T细胞和B细胞时，vav-/- T细胞反应低下，但暴露于磷酸酯和钙离子载体时，vav-/- T细胞增殖15，而B细胞对细菌有丝分裂原、脂多糖或CD40配体反应正常16 - 18。因此，我们在这里确定了vav在控制t细胞和b细胞发育和激活中的功能作用。
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.
影响因子：
11.4
作者：
KATZAV, S;MARTINZANCA, D;BARBACID, M
通讯作者：
BARBACID, M
DOI：
10.1073/pnas.89.14.6550
发表时间：
1992-07-15
影响因子：
11.1
作者：
NOELLE, RJ;ROY, M;ARUFFO, A
通讯作者：
ARUFFO, A
DOI：
10.1073/pnas.90.10.4528
发表时间：
1993-05-15
影响因子：
11.1
作者：
CHEN, JZ;LANSFORD, R;ALT, FW
通讯作者：
ALT, FW