Vav family proteins couple to diverse cell surface receptors

作     者：Moores, SL Selfors, LM Fredericks, J Breit, T Fujikawa, K Alt, FW Brugge, JS Swat, W 

作者机构：Harvard Univ Sch Med Dept Cell Biol Boston MA 02115 USA Harvard Univ Sch Med Dept Genet Boston MA 02115 USA Harvard Univ Sch Med Ctr Blood Res Boston MA 02115 USA Harvard Univ Sch Med Dept Pediat Childrens Hosp Boston MA 02115 USA Harvard Univ Sch Med Howard Hughes Med Inst Boston MA 02115 USA 

出 版 物：《MOLECULAR AND CELLULAR BIOLOGY》 (分子生物学与细胞生物学)

年 卷 期：2000年第20卷第17期

页      面：6364-6373页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 07[理学] 

基　　金：NCI NIH HHS [CA78773, R01 CA078773] Funding Source: Medline NHLBI NIH HHS [P01 HL59561, P01 HL059561] Funding Source: Medline NIAID NIH HHS [R37 AI020047, R01 AI020047, AI20047] Funding Source: Medline 

主　　题：氨基酸序列 CHO细胞 COS细胞 细胞周期蛋白质类 细胞系 仓鼠亚科 DNA 互补/代谢 表皮生长因子/药理学 鸟嘌呤核苷酸交换因子类 整合素类/代谢 Jurkat细胞 分子序列数据 癌基因蛋白质类/化学 癌基因蛋白质类/代谢 磷酰化 血小板源性生长因子/药理学 蛋白质结合 蛋白质亚型 蛋白质结构 三级 原癌基因蛋白质类/化学 原癌基因蛋白质类/代谢 原癌基因蛋白质c-vav 受体 抗原 B细胞/代谢 受体 抗原 T细胞/代谢 受体 细胞表面/代谢 序列同源性 氨基酸 信号传导 酪氨酸/代谢 动物 人类 小鼠 

摘      要：Vav proteins are guanine nucleotide exchange factors for Rho family GTPases which activate pathways leading to actin cytoskeletal rearrangements and transcriptional alterations. Vav proteins contain several protein binding domains which can link cell surface receptors to downstream signaling proteins. Vav1 is expressed exclusively in hematopoietic cells and tyrosine phosphorylated in response to activation of multiple cell surface receptors. However, it is not known whether the recently identified isoforms Vav2 and Vav3, which are broadly expressed, can couple,vith similar classes of receptors, nor is it known whether all Vav isoforms possess identical functional activities. We expressed Vav1, Vav2, and Vav3 at equivalent levels to directly compare the responses of the Vav proteins to receptor activation. Although each Vav isoform was tyrosine phosphorylated upon activation of representative receptor tyrosine kinases, integrin, and lymphocyte antigen receptors, we found unique aspects of Vav protein coupling in each receptor pathway. Each Vav protein coprecipitated with activated epidermal growth factor and platelet-derived growth factor (PDGF) receptors, and multiple phosphorylated tyrosine residues on the PDGF receptor were able to mediate Vav2 tyrosine phosphorylation, Integrin-induced tyrosine phosphorylation of Vav proteins was net detected in nonhematopoietic cells unless the protein tyrosine kinase Syk was also expressed, suggesting that integrin activation of Vav proteins may be restricted to cell types that express particular tyrosine kinases. In addition, we found that Vav1, but not Vav2 or Vav3, can efficiently cooperate with T-cell receptor signaling to enhance NFAT dependent transcription, while Vav1 and Vav3, but not Vav2, can enhance NF kappa B dependent transcription. Thus, although each Vav isoform can respond to similar cell surface receptors, there are isoform-specific differences in their activation of downstream signaling pathways.