A novel signaling intermediate, SHEP1, directly couples Eph receptors to R-Ras and Rap1A

作     者：Dodelet, VC Pazzagli, C Zisch, AH Hauser, CA Pasquale, EB 

作者机构：Burnham Inst La Jolla CA 92037 USA 

出 版 物：《JOURNAL OF BIOLOGICAL CHEMISTRY》 (生物化学杂志)

年 卷 期：1999年第274卷第45期

页      面：31941-31946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：NICHD NIH HHS [HD26351  HD25938] Funding Source: Medline 

主　　题：衔接蛋白质类 信号转导 氨基酸序列 载体蛋白质类/化学 载体蛋白质类/代谢 细胞系 克隆 分子 GTP磷酸水解酶类/代谢 基因文库 分子序列数据 神经组织蛋白质类/化学 神经组织蛋白质类/代谢 聚合酶链反应 受体蛋白质酪氨酸激酶类/代谢 受体 EphB2 信号传导 rap1GTP结合蛋白质类/代谢 ras蛋白质类/代谢 动物 人类 小鼠 兔 

摘      要：The Eph family of receptor tyrosine kinases has been implicated in many developmental patterning processes, including cell segregation, cell migration, and axon guidance. The cellular components involved in the signaling pathways of the Eph receptors, however, are incompletely characterized. Using a yeast two-hybrid screen, we have identified a novel signaling intermediate, SHEP1 (SH2 domain-containing Eph receptor-binding protein 1), which is expressed in the embryonic and adult brain. SHEP1 contains an Src homology 2 domain that binds to a conserved tyrosine-phosphorylated motif in the juxtamembrane region of the EphB2 receptor and may itself be a target of EphB2 kinase activity, since it becomes heavily tyrosine-phosphorylated in cells expressing activated EphB2, SHEP1 also contains a domain similar to Ras guanine nucleotide exchange factor domains and binds to the GTPases R-Ras and Rap1A, but not Ha-Ras or Ra1A, Thus, SHEP1 directly links activated, tyrosine-phosphorylated Eph receptors to small Ras superfamily GTPases.