Bonnefoy-Bérard N, Munshi A, Yron I, Wu S, Collins T L, Deckert M, Shalom-Barak T, Giampa L, Herbert E, Hernandez J, Meller N, Couture C, Altman A
INSERM U80, Hôpital E. Herriot, Lyon, France.
Stem Cells. 1996 May;14(3):250-68. doi: 10.1002/stem.140250.
Vav, a 95 kDa proto-oncogene product expressed specifically in hematopoietic cells, was originally isolated as a transforming human oncogene. Vav contains an array of functional domains that are involved in interactions with other proteins and, possibly, with lipids. These include, among others, a putative guanine nucleotide exchange domain, a cysteine-rich region similar to the phorbol ester/diacylglycerol-binding domain of protein kinase C, a pleckstrin-homology domain, and Src-homology 2 and 3 (SH2 and SH3, respectively) domains. The presence of these domains, the transforming activity of the vav oncogene, and the rapid increase in tyrosine phosphorylation of Vav induced by triggering of diverse receptors indicate that it plays an important role in hematopoietic cell signaling pathways. Such a role is supported by recent studies using "knockout" mice and transiently transfected T cells, in which Vav deletion or overexpression, respectively, had marked effects on lymphocyte development or activation. The presence of a putative guanine nucleotide exchange domain, the prototype of which is found in the dbl oncogene product, implies that Vav functions as a guanine nucleotide exchange factor (GEF) for one (or more) members of the Ras-like family of small GTP-binding proteins. In support of such a role, Vav preparations were found in some (but not other) studies to mediate in vitro-specific GEF activity for Ras. Additional studies are required to identify the physiological regulators and targets of Vav, and its exact role in hematopoietic cell development and signaling.
Vav是一种95 kDa的原癌基因产物，在造血细胞中特异性表达，最初作为一种转化型人类癌基因被分离出来。Vav包含一系列功能结构域，这些结构域参与与其他蛋白质以及可能与脂质的相互作用。其中包括一个假定的鸟嘌呤核苷酸交换结构域、一个与蛋白激酶C的佛波酯/二酰基甘油结合结构域相似的富含半胱氨酸的区域、一个普列克底物蛋白同源结构域以及Src同源2和3（分别为SH2和SH3）结构域。这些结构域的存在、vav癌基因的转化活性以及多种受体触发后Vav酪氨酸磷酸化的快速增加表明，它在造血细胞信号通路中起重要作用。最近使用“基因敲除”小鼠和瞬时转染T细胞的研究支持了这一作用，其中Vav缺失或过表达分别对淋巴细胞发育或激活有显著影响。一个假定的鸟嘌呤核苷酸交换结构域的存在，其原型存在于dbl癌基因产物中，这意味着Vav作为一种鸟嘌呤核苷酸交换因子（GEF）作用于小GTP结合蛋白的Ras样家族中的一个（或多个）成员。为支持这一作用，在一些（但不是其他）研究中发现Vav制剂可介导Ras的体外特异性GEF活性。还需要进一步研究来确定Vav的生理调节因子和靶点，以及它在造血细胞发育和信号传导中的确切作用。
