Bundschu Karin, Walter Ulrich, Schuh Kai
Abteilung Biochemie und Molekulare Biologie, Universität Ulm, Ulm, Germany.
Bioessays. 2007 Sep;29(9):897-907. doi: 10.1002/bies.20632.
Spreds form a new protein family with an N-terminal Enabled/VASP homology 1 domain (EVH1), a central c-Kit binding domain (KBD) and a C-terminal Sprouty-related domain (SPR). They are able to inhibit the Ras-ERK signalling pathway after various mitogenic stimulations. In mice, Spred proteins are identified as regulators of bone morphogenesis, hematopoietic processes, allergen-induced airway eosinophilia and hyperresponsiveness. They inhibit cell motility and metastasis and have a high potential as tumor markers and suppressors of carcinogenesis. Moreover, in vertebrates, XtSpreds help together with XtSprouty proteins to coordinate gastrulation and mesoderm specification. Here, we give an overview of this new field and summarize the domain functions, binding partners, expression patterns and the cellular localizations, regulations and functions of Spred proteins and try to give perspectives for future scientific directions.
Spreds 构成了一个新的蛋白质家族,具有 N 端 Enabled/VASP 同源 1 结构域(EVH1)、一个中央 c-Kit 结合结构域(KBD)和一个 C 端 Sprouty 相关结构域(SPR)。在各种促有丝分裂刺激后,它们能够抑制 Ras-ERK 信号通路。在小鼠中,Spred 蛋白被鉴定为骨形态发生、造血过程、变应原诱导的气道嗜酸性粒细胞增多和高反应性的调节因子。它们抑制细胞运动和转移,具有作为肿瘤标志物和癌症发生抑制因子的巨大潜力。此外,在脊椎动物中,XtSpreds 与 XtSprouty 蛋白共同帮助协调原肠胚形成和中胚层特化。在此,我们对这个新领域进行概述,并总结 Spred 蛋白的结构域功能、结合伴侣、表达模式、细胞定位、调控和功能,并尝试为未来的科学方向提供展望。