Gulbins E, Langlet C, Baier G, Bonnefoy-Berard N, Herbert E, Altman A, Coggeshall K M
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, CA 92037.
J Immunol. 1994 Mar 1;152(5):2123-9.
Ag receptor triggering in B cells stimulates the activity of receptor-associated tyrosine protein kinases (TPK), leading to tyrosine phosphorylation of several cellular substrates, one of which is the Vav proto-oncogene product. We have recently determined that Vav is a TPK-regulated guanine nucleotide exchange factor for Ras in T cells. Here, we show that B cell extracts or Vav immunoprecipitates contain a Ras GDP/GTP exchange activity that is stimulated upon surface Ig (slg) triggering. The receptor-mediated stimulation of Vav exchange activity was blocked by the TPK antagonist, herbimycin A. Furthermore, immunodepletion of Vav from the B cell extracts removed approximately 80% of the Ras GDP/GTP exchange activity. These findings indicate, first, that B cell-derived Vav possesses GDP/GTP exchange activity for Ras; second, that the exchange activity of Vav is accelerated by a slg-triggered, herbimycin A-sensitive TPK and, third, that Vav accounts for most of the receptor-stimulated Ras GDP/GTP exchange activity. Thus, Vav may serve as a critical component in slg-mediated signal transduction pathways by coupling receptor-associated TPK to the activation of Ras proteins.
B细胞中的抗原受体触发可刺激受体相关酪氨酸蛋白激酶（TPK）的活性，导致几种细胞底物发生酪氨酸磷酸化，其中之一是Vav原癌基因产物。我们最近确定，Vav是T细胞中一种受TPK调节的Ras鸟嘌呤核苷酸交换因子。在此，我们表明B细胞提取物或Vav免疫沉淀物含有一种Ras GDP/GTP交换活性，该活性在表面Ig（slg）触发时会被刺激。TPK拮抗剂赫曲霉素A可阻断受体介导的Vav交换活性刺激。此外，从B细胞提取物中免疫去除Vav可使Ras GDP/GTP交换活性降低约80%。这些发现表明，首先，B细胞来源的Vav具有针对Ras的GDP/GTP交换活性；其次，Vav的交换活性可被slg触发的、对赫曲霉素A敏感的TPK加速；第三，Vav占受体刺激的Ras GDP/GTP交换活性的大部分。因此，Vav可能通过将受体相关TPK与Ras蛋白的激活相偶联，而成为slg介导的信号转导途径中的关键成分。
