Vav1: A hematopoietic signal transduction molecule involved in human malignancies
Vav1: A hematopoietic signal transduction molecule involved in human malignancies
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DOI：
10.1016/j.biocel.2008.11.006
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发表时间：
2009-06-01
影响因子：
4
通讯作者：
Katzav, Shulamit
中科院分区：
文献类型：
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作者：
Katzav, Shulamit
Vav1编码一种独特的蛋白，其具有几个已知在酪氨酸介导的信号转导中起作用的基元，包括DBL同源（DH）结构域、pleckstrin同源（PH）结构域、Src同源2 （SH2）结构域和两个Src同源3 （SH3）结构域。生理上Vav1的表达仅限于造血系统，在造血系统中，它主要作为一种特定的GDP/GTP核苷酸交换因子（GEF）发挥作用，这种功能受到酪氨酸磷酸化的严格调节。在造血细胞中，Vav1在细胞表面受体激活后被磷酸化，触发细胞骨架重组并调节其他细胞功能，包括转录、细胞因子产生、细胞周期进程和Ca（2+）动员。Vav1还作为适配器，促进其他蛋白质之间的相互作用。截断的Vav1首次被分离为致癌基因，其野生型最近与哺乳动物恶性肿瘤有关。这些特性使Vav1成为器官移植和癌症治疗新方法的一个有希望的靶点。(C) 2008 Elsevier Ltd版权所有。
Vav1 encodes a unique protein with several motifs known to play a role in tyrosine mediated signal transduction, including a DBL homology (DH) domain, a pleckstrin homology (PH) domain, a Src homology 2 (SH2) domain, and two Src homology 3 (SH3) domains. Physiological Vav1 expression is restricted to the hematopoietic system, where it functions primarily as a specific GDP/GTP nucleotide exchange factor (GEF), a function strictly regulated by tyrosine phosphorylation. In hematopoietic cells, Vav1 is phosphorylated following cell surface receptor activation, triggering re-organization of the cytoskeleton and regulation of other cellular functions including transcription, cytokine production, cell cycle progression, and Ca(2+) mobilization. Vav1 also functions as an adapter, facilitating interaction between other proteins. A truncated Vav1 was first isolated as an oncogene, and its wild-type form has recently been implicated in mammalian malignancies. These properties make Vav1 a promising target for new therapeutic approaches to organ transplantation and cancer therapy. (C) 2008 Elsevier Ltd. All rights reserved.