The roles of SPRED proteins in signaling, development, and cancer are becoming increasingly recognized. SPRED proteins comprise an N-terminal EVH-1 domain, a central c-Kit-binding domain, and C-terminal SROUTY domain. They negatively regulate signaling from tyrosine kinases to the Ras–MAPK pathway. SPRED1 binds directly to both c-KIT and to the RasGAP, neurofibromin, whose function is completely dependent on this interaction. Loss-of-function mutations in SPRED1 occur in human cancers and cause the developmental disorder, Legius syndrome. Genetic ablation of SPRED genes in mice leads to behavioral problems, dwarfism, and multiple other phenotypes including increased risk of leukemia. In this review, we summarize and discuss biochemical, structural, and biological functions of these proteins including their roles in normal cell growth and differentiation and in human disease.

中文翻译：

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SPRED 蛋白及其在信号转导、发育和恶性肿瘤中的作用

SPRED 蛋白在信号传导、发育和癌症中的作用日益得到认可。SPRED 蛋白包含 N 端 EVH-1 结构域、中央 c-Kit 结合结构域和 C 端 SROUTY 结构域。它们负向调节从酪氨酸激酶到 Ras-MAPK 通路的信号传导。SPRED1 直接与 c-KIT 和 RasGAP（神经纤维蛋白）结合，其功能完全依赖于这种相互作用。SPRED1 的功能丧失突变发生在人类癌症中，并导致发育障碍、Legius 综合征。小鼠 SPRED 基因的基因消除会导致行为问题、侏儒症和多种其他表型，包括增加白血病风险。在这篇综述中，我们总结并讨论了这些蛋白质的生化、结构和生物学功能，包括它们在正常细胞生长和分化以及人类疾病中的作用。