Curtis B M, Williams D E, Broxmeyer H E, Dunn J, Farrah T, Jeffery E, Clevenger W, deRoos P, Martin U, Friend D
Immunex Research and Development Corporation, Seattle, WA 98101.
Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5809-13. doi: 10.1073/pnas.88.13.5809.
Granulocyte/macrophage colony-stimulating factor-interleukin 3 (GM-CSF-IL-3) fusion proteins were generated by construction of a plasmid in which the coding regions of human GM-CSF and IL-3 cDNAs were connected by a synthetic linker sequence followed by subsequent expression in yeast. Both GM-CSF-IL-3 and IL-3-GM-CSF fusion proteins were purified to homogeneity and shown to bind to cell-surface receptors through either their GM-CSF or IL-3 domains. The fusion proteins exhibited enhanced receptor affinity, proliferative activity, and hematopoietic colony-stimulating activity compared with either IL-3 and/or GM-CSF alone. This suggests that GM-CSF-IL-3 fusion proteins may hold future promise as therapeutic agents.
粒细胞/巨噬细胞集落刺激因子-白细胞介素3(GM-CSF-IL-3)融合蛋白是通过构建一种质粒产生的,该质粒中人类GM-CSF和IL-3的cDNA编码区由一个合成接头序列连接,随后在酵母中表达。GM-CSF-IL-3和IL-3-GM-CSF融合蛋白均被纯化至同质,并显示通过其GM-CSF或IL-3结构域与细胞表面受体结合。与单独的IL-3和/或GM-CSF相比,融合蛋白表现出增强的受体亲和力、增殖活性和造血集落刺激活性。这表明GM-CSF-IL-3融合蛋白作为治疗剂可能具有未来前景。